from Journal of the American Society of Nephrology current issue http://ift.tt/2t5bY...
Wednesday, February 28, 2018
The Era of Human Developmental Nephrology
from Journal of the American Society of Nephrology current issue http://ift.tt/2F1I2...
Evolution and Kidney Development: A Rosetta Stone for Nephrology
from Journal of the American Society of Nephrology current issue http://ift.tt/2F2UL...
The Benefits of Tubular Proteinuria: An Evolutionary Perspective
from Journal of the American Society of Nephrology current issue http://ift.tt/2t2RN...
The UMOD Locus: Insights into the Pathogenesis and Prognosis of Kidney Disease
The identification of genetic factors associated with kidney disease has the potential to provide critical insights into disease mechanisms. Genome-wide association studies have uncovered genomic regions associated with renal function metrics and risk of CKD. UMOD is among the most outstanding loci associated with CKD in the general population, because it has a large effect on eGFR and CKD risk that is consistent across different ethnic groups. The...
Salt-Losing Tubulopathies in Children: Whats New, Whats Controversial?
Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual...
Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives
The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and...
Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach
FSGS describes a renal histologic lesion with diverse causes and pathogenicities that are linked by podocyte injury and depletion. Subclasses of FSGS include primary, genetic, and secondary forms, the latter comprising maladaptive, viral, and drug-induced FSGS. Despite sharing certain clinical and histologic features, these subclasses differ noticeably in management and prognosis. Without an accepted nongenetic biomarker that discriminates among...
Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion
The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic...
Conserved and Divergent Features of Human and Mouse Kidney Organogenesis
Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34–37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited...
Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney
Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2+ nephron progenitor cells (NPCs) and Foxd1+ interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization,...
Conserved and Divergent Molecular and Anatomic Features of Human and Mouse Nephron Patterning
The nephron is the functional unit of the kidney, but the mechanism of nephron formation during human development is unclear. We conducted a detailed analysis of nephron development in humans and mice by immunolabeling, and we compared human and mouse nephron patterning to describe conserved and divergent features. We created protein localization maps that highlight the emerging patterns along the proximal–distal axis of the developing nephron and...
Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney
Tamm–Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial...
GRHL2 Is Required for Collecting Duct Epithelial Barrier Function and Renal Osmoregulation
Collecting ducts make up the distal-most tubular segments of the kidney, extending from the cortex, where they connect to the nephron proper, into the medulla, where they release urine into the renal pelvis. During water deprivation, body water preservation is ensured by the selective transepithelial reabsorption of water into the hypertonic medullary interstitium mediated by collecting ducts. The collecting duct epithelium forms tight junctions...
ApoL1 Overexpression Drives Variant-Independent Cytotoxicity
Coding variants in the APOL1 gene are associated with kidney diseases in African ancestral populations; yet, the underlying biologic mechanisms remain uncertain. Variant-dependent autophagic and cytotoxic cell death have been proposed as pathogenic pathways mediating kidney injury. To examine this possibility, we conditionally expressed APOL1-G0 (reference), -G1, and -G2 (variants) using a tetracycline-regulated system in HEK293 cells. Autophagy...
Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction
Increased export of transglutaminase-2 (TG2) by tubular epithelial cells (TECs) into the surrounding interstitium modifies the extracellular homeostatic balance, leading to fibrotic membrane expansion. Although silencing of extracellular TG2 ameliorates progressive kidney scarring in animal models of CKD, the pathway through which TG2 is secreted from TECs and contributes to disease progression has not been elucidated. In this study, we developed...
Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling
In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1,...
Exosomal CCL2 from Tubular Epithelial Cells Is Critical for Albumin-Induced Tubulointerstitial Inflammation
Albuminuria is a key instigator of tubulointerstitial inflammation associated with CKD, but the mechanism through which filtered albumin propagates renal injury remains unclear. In this study, we explored the role in this process of exosome mRNA released from tubular epithelial cells (TECs). Compared with control mice, acute and chronic kidney injury models had more exosomes containing inflammatory cytokine mRNA, particularly the chemokine CCL2,...
CHIP Regulates Aquaporin-2 Quality Control and Body Water Homeostasis
The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins have a regulatory role in these cells and how these cells can be regulated by individual physiologic stimuli. By combining proteomics, bioinformatics,...
Pathogenicity of a Human Laminin {beta}2 Mutation Revealed in Models of Alport Syndrome
Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β2 (LAMB2), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation,...
Potentiating Tissue-Resident Type 2 Innate Lymphoid Cells by IL-33 to Prevent Renal Ischemia-Reperfusion Injury
The IL-33-type 2 innate lymphoid cell (ILC2) axis has an important role in tissue homeostasis, inflammation, and wound healing. However, the relative importance of this innate immune pathway for immunotherapy against inflammation and tissue damage remains unclear. Here, we show that treatment with recombinant mouse IL-33 prevented renal structural and functional injury and reduced mortality in mice subjected to ischemia-reperfusion injury (IRI)....
Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific {gamma}ENaC Knockout
The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific...
Magnesium and Risk of Hip Fracture among Patients Undergoing Hemodialysis
Magnesium is an essential mineral for bone metabolism. However, little is known about the relationship between magnesium and the risk of fractures. In this cohort study, we elucidated the association between serum magnesium level and the risk of incident hip fracture among patients undergoing hemodialysis. We identified 113,683 patients undergoing hemodialysis with no history of hip fracture from a nation-wide database of patients undergoing dialysis...
Causes of Death after a Hospitalization with AKI
Mortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital...
Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI
Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization...
Maternal and Fetal Outcomes of Pregnancies in Women with Atypical Hemolytic Uremic Syndrome
Atypical HUS (aHUS) is a disorder most commonly caused by inherited defects of the alternative pathway of complement, or the proteins that regulate this pathway, and life-threatening episodes of aHUS can be provoked by pregnancy. We retrospectively and prospectively investigated 27 maternal and fetal pregnancy outcomes in 14 women with aHUS from the Vienna Thrombotic Microangiopathy Cohort. Seven pregnancies (26%) were complicated by pregnancy-associated...
Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous Fistulas
The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation....
Acidosis and Deafness in Patients with Recessive Mutations in FOXI1
Maintenance of the composition of inner ear fluid and regulation of electrolytes and acid-base homeostasis in the collecting duct system of the kidney require an overlapping set of membrane transport proteins regulated by the forkhead transcription factor FOXI1. In two unrelated consanguineous families, we identified three patients with novel homozygous missense mutations in FOXI1 (p.L146F and p.R213P) predicted to affect the highly conserved DNA...
Control of Humoral Response in Renal Transplantation by Belatacept Depends on a Direct Effect on B Cells and Impaired T Follicular Helper-B Cell Crosstalk
Generation of de novo donor-specific antibodies (dnDSAs) after renal transplant is recognized as the leading cause of late transplant failure. Hence, the optimal immunosuppressive strategies to limit dnDSA development need to be defined. Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig (Belatacept) have shown that kidney transplant recipients (KTRs) treated with Belatacept have better graft survival and function and a...
Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with Thrombosis after Vascular Injury in Humans
Individuals with CKD are particularly predisposed to thrombosis after vascular injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan metabolite retained in CKD and an activator of tissue factor (TF) through aryl hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD spectrum. However, the translation of findings from animal models to humans is often challenging. Here, we investigated the uremic...
FOX NEWS: Another reason to worry about overcrowded emergency rooms
Another reason to worry about overcrowded emergency rooms
Patients are more likely to be misdiagnosed or experience treatment delays when emergency rooms are so crowded that they receive care in a hallway, a survey of physicians suggest...
FOX NEWS: Teen who was told he had the flu, really had stage 4 cancer
Teen who was told he had the flu, really had stage 4 cancer
A teenager from Tampa, Florida who was told her had the flu discovers he is battling stage 4 cance...
FOX NEWS: Obese high school student who attempted suicide drops 157 pounds
Obese high school student who attempted suicide drops 157 pounds
An obese high school student makes a turnaround after attempting suicide, and decides to have weight-loss surgery and loses 157 pound...
FOX NEWS: Popular Alaska peak weighs new rules for climbers' poop
Popular Alaska peak weighs new rules for climbers' poop
Climbers on North America's tallest mountain may have to start packing out more of their poop after a researcher determined a glacier in which much of it has been dumped over the past decade probably is not decomposing the human wast...
FOX NEWS: What's in the IV bag? Studies show safer option than saline
What's in the IV bag? Studies show safer option than saline
Two large studies found that using a different intravenous fluid instead of the usual saline significantly reduced the risk of death or kidney damag...
FOX NEWS: The Spice Diet: A diet that explodes with flavor ... and happens to be healthy
The Spice Diet: A diet that explodes with flavor ... and happens to be healthy
The Spice Diet breaks down what spices to pair with specific ingredients to yield a dish that explodes with flavor and that just so happens to be very healthy for yo...
FOX NEWS: Former Yankees GM refuses kidney donation offers from his children
Former Yankees GM refuses kidney donation offers from his children
A former New York Yankees general manager turned his children’s offers to donate a new kidney as he battles kidney failur...
Tuesday, February 27, 2018
FOX NEWS: U.S. to file 'statement of interest' in lawsuits against opioid makers, distributors
U.S. to file 'statement of interest' in lawsuits against opioid makers, distributors
The United States will file a "statement of interest" in an action involving hundreds of lawsuits against drug manufacturers and distributors, U.S. Attorney General Jeff Sessions said on Tuesda...
FOX NEWS: Aerobic exercise slows cognitive decline in Alzheimer's disease
Aerobic exercise slows cognitive decline in Alzheimer's disease
Cardiovascular exercise training may help slow the decline in brain function seen in Alzheimer's patients, a new review of past research suggest...
FOX NEWS: Standing desks may be harmful to your health, according to new study
Standing desks may be harmful to your health, according to new study
New research suggests that using standing desks for a prolonged period of time will create "discomfort and deteriorating mental reactiveness...
FOX NEWS: Too much tech: Today's kids struggle to hold pencils, study says
Too much tech: Today's kids struggle to hold pencils, study says
Overuse of touchscreen phones and tablets is preventing children's finger muscles from developing so they can properly hold a pencil says a new repor...
FOX NEWS: Teen sexting may be more common than you think
Teen sexting may be more common than you think
At least one in four teens are receiving sexually explicit texts and emails, and at least one in seven are sending sexts, a new study suggest...
FOX NEWS: Woman's hand that was chopped off in machine was saved by co-workers
Woman's hand that was chopped off in machine was saved by co-workers
A woman has miraculously regained the use of her hand after it was completely severed by a coconut chopping machin...
Sneeze Into Your Elbow, Not Your Hand. Please.
By DANIEL VICTOR from NYT Health http://ift.tt/2HMKv...
Monday, February 26, 2018
FOX NEWS: Mom 'fighting for her life' in ICU after contracting rare, rodent-carried Hantavirus
Mom 'fighting for her life' in ICU after contracting rare, rodent-carried Hantavirus
In early January, Kiley Lane went to the hospital for what she thought was the fl...
FOX NEWS: Pediatricians issue new guidelines for depression screening for teens
Pediatricians issue new guidelines for depression screening for teens
The American Academy of Pediatrics has issued updated guidelines that call for universal screening for depressio...
F.D.A. to Expand Medication-Assisted Therapy for Opioid Addicts
By SHEILA KAPLAN from NYT Health http://ift.tt/2HLBe...
FOX NEWS: Childhood obesity is worse among 2-5 year olds
Childhood obesity is worse among 2-5 year olds
New data published in the journal Pediatrics reports that childhood obesity is not improving, and actually rose from 9-14% since 199...
FOX NEWS: Supermodel Niki Taylor opens up about the heart disease that killed her sister
Supermodel Niki Taylor opens up about the heart disease that killed her sister
In a rare interview, supermodel Niki Taylor opens up about losing her younger sister, Krissy Taylor, to heart disease and why she’s raising awareness 23 years after her tragic deat...
FOX NEWS: Fertility doctor's secret reveals discovery of at least 23 half-siblings
Fertility doctor's secret reveals discovery of at least 23 half-siblings
After Dr. Donald Cline received a one-year suspended sentence for lying when denied being a sperm donor to unwitting patients, a special bond has formed between half-siblings decades late...
Sunday, February 25, 2018
FOX NEWS: Tourist infected with measles went to New York art museum, area hotels, health officials say
Tourist infected with measles went to New York art museum, area hotels, health officials say
An Australian tourist infected with measles visited several locations in New York City, included the famed The Metropolitan Museum of Art, health officials warned Saturda...
Friday, February 23, 2018
FOX NEWS: Fake urine: Mississippi in legislative push to flush it away
Fake urine: Mississippi in legislative push to flush it away
Political and business leaders in Mississippi are working to pass a law that would flush fake urine down the toilet. The Mississippi Urine Trouble Act would ban the sale or use of synthetic human urine for the purposes of defrauding a drug tes...
FOX NEWS: Fake Urine: Mississippi lawmakers say flush it away
Fake Urine: Mississippi lawmakers say flush it away
Political and business leaders in Mississippi are working to pass a law that would flush fake urine down the toilet The Mississippi Urine Trouble Act would ban the sale or use of synthetic human urine for the purposes of defrauding a drug tes...
FOX NEWS: Martin Shkreli controversies: A timeline of events
Martin Shkreli controversies: A timeline of events
Martin Shkreli, the former biotech CEO known for hiking up the price of a life-saving drug, was convicted on federal charges he deceived investors in a pair of failed hedge fund...
FOX NEWS: Potentially toxic chemicals were found in e-cigarette vaper
Potentially toxic chemicals were found in e-cigarette vaper
A significant number of e-cigarette devices produced aerosols with potentially dangerous levels of lead, as well as other metals like chromium, manganese, and nickel which could cause cance...
Patients Eagerly Awaited a Generic Drug. Then They Saw the Price.
By KATIE THOMAS from NYT Health http://ift.tt/2sOiw...
FOX NEWS: Young men's drinking tied to later liver disease risk
Young men's drinking tied to later liver disease risk
Researchers found that a percentage of men who drank heavily in their younger years developed severe liver disease later in lif...
FOX NEWS: Nasty flu season showing signs of winding down
Nasty flu season showing signs of winding down
U.S. health officials say fewer visits to the doctor last week — 1 out of 16 — were for fever, cough and other flu symptoms than during the previous two weeks. The number of states reporting high patient traffic for the flu also dropped, to 39 from 4...
FOX NEWS: One-third of millennials brush teeth just once a day, study shows
One-third of millennials brush teeth just once a day, study shows
A new survey of 2000 people shows that 30% of millennials only brush their teeth once a da...
Measles Cases in Europe Quadrupled in 2017
By DONALD G. McNEIL Jr. from NYT Health http://ift.tt/2oo2o...
Thursday, February 22, 2018
Opening Mental Hospitals Unlikely to Prevent Mass Shootings, Experts Say
By BENEDICT CAREY from NYT Health http://ift.tt/2HEhL...
FOX NEWS: Bubble parade for boy who survives bone marrow transplant
Bubble parade for boy who survives bone marrow transplant
Hospital staff at Boston Children's Hospital throw a "bubble parade" for a boy who was discharged after a grueling bone marrow transplan...
FOX NEWS: YouTube star who claims veganism healed her breast cancer dies from disease
YouTube star who claims veganism healed her breast cancer dies from disease
Mari Lopez, who hosted a YouTube channel, died from breast cancer after claiming her vegan and spiritual lifestyle cured her of the diseas...
FOX NEWS: Doctors successfully remove 4-pound brain tumor, bigger than head itself
Doctors successfully remove 4-pound brain tumor, bigger than head itself
Surgeons in India successfully removed a 4 pound tumor from a 31 year old ma...
Wednesday, February 21, 2018
FOX NEWS: Florida House declares porn a public health risk
Florida House declares porn a public health risk
Florida lawmakers on Tuesday declared pornography a health risk, and called for more research on its affect...
FOX NEWS: Healthy food blogger almost died from dieting obsession
Healthy food blogger almost died from dieting obsession
A woman was so obsessed with posting pictures of superfoods, she ended up with an eating disorde...
FOX NEWS: Parents say amazing ultrasound shows unborn baby giving V-sign
Parents say amazing ultrasound shows unborn baby giving V-sign
An amazing 4D scan shows an unborn baby giving the V-sign to his parents when they suggested a nam...
FOX NEWS: Herbal drug kratom is linked to salmonella illnesses, CDC says
Herbal drug kratom is linked to salmonella illnesses, CDC says
The popular botanical drug kratom is being linked to salmonella according to the Centers for Disease Control and Preventio...
FOX NEWS: Parents say amazing scan shows unborn baby giving V-sign
Parents say amazing scan shows unborn baby giving V-sign
An amazing 4D scan shows an unborn baby giving the V-sign to his parents when they suggested a nam...
FOX NEWS: Heart alert: Pacemakers can be hacked, new research shows
Heart alert: Pacemakers can be hacked, new research shows
There is a possibility that pacemakers and other electrical devices could be targeted by hackers, according to a paper published in the Journal of American College of Cardiolog...
FOX NEWS: Florida House declares pornography a public health risk
Florida House declares pornography a public health risk
Florida lawmakers on Tuesday declared pornography a health risk, and called for more research on its affect...
Tuesday, February 20, 2018
FOX NEWS: Florida House declares pornography a public health risk
Florida House declares pornography a public health risk
Florida lawmakers on Tuesday declared pornography a health risk, and called for more research on its affect...
Comment on "{gamma}{delta} T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations" [LETTERS TO THE EDITOR]
from The Journal of Immunology current issue http://ift.tt/2BJ14...
Response to Comment on "{gamma}{delta} T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations" [LETTERS TO THE EDITOR]
from The Journal of Immunology current issue http://ift.tt/2C9n2...
The Chemical Elucidation of Slow-Reacting Substance: Bronchospasm and Beyond [PILLARS OF IMMUNOLOGY]
from The Journal of Immunology current issue http://ift.tt/2olYj...
Pillars Article: Leukotriene C: A Slow-Reacting Substance from Murine Mastocytoma Cells. Proc. Natl. Acad. Sci. USA. 1979. 76: 4275-4279 [PILLARS OF IMMUNOLOGY]
from The Journal of Immunology current issue http://ift.tt/2C7xc...
Sepsis-Induced T Cell Immunoparalysis: The Ins and Outs of Impaired T Cell Immunity [BRIEF REVIEWS]
Sepsis results in a deluge of pro- and anti-inflammatory cytokines, leading to lymphopenia and chronic immunoparalysis. Sepsis-induced long-lasting immunoparalysis is defined, in part, by impaired CD4 and CD8 αβ T cell responses in the postseptic environment. The dysfunction in T cell immunity affects naive, effector, and memory T cells and is not restricted to classical αβ T cells. Although sepsis-induced severe and transient lymphopenia is a contributory...
Cutting Edge: Nqo1 Regulates Irritant Contact Hypersensitivity against Croton Oil through Maintenance of Dendritic Epidermal T Cells [CUTTING EDGE]
Irritant contact dermatitis (ICD) is associated with local release of inflammatory mediators such as reactive oxygen species and regulated by various antioxidative enzymes and antioxidants. Although Nqo1 is involved in antioxidative reactions and detoxification, its role in ICD remains unknown. Nqo1-deficient mice exhibited augmented ear swelling accompanied by neutrophil infiltration in the croton oil–induced mouse ICD model. In the skin of Nqo1-deficient...
Biased Generation and In Situ Activation of Lung Tissue-Resident Memory CD4 T Cells in the Pathogenesis of Allergic Asthma [ALLERGY AND OTHER HYPERSENSITIVITIES]
Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T cells that promote lung inflammation through recruitment of cellular effectors into the lung. A subset of lung T cells can persist as tissue-resident memory T cells (TRMs) following infection and allergen induction, although the generation and role of TRM in asthma persistence and pathogenesis remain unclear. In this study, we used a mouse model of chronic exposure to intranasal...
Therapeutic Application of an Extract of Helicobacter pylori Ameliorates the Development of Allergic Airway Disease [ALLERGY AND OTHER HYPERSENSITIVITIES]
Epidemiological and experimental studies have shown that exposure to the gastric bacterium Helicobacter pylori, especially in early life, prevents the development of asthma. Recent mouse studies have shown that this protective effect does not require live bacteria and that treatment with an extract of H. pylori in neonates prevents the development of airway inflammation and goblet cell metaplasia. In the current study, the effect of administration...
IL-10 Paradoxically Promotes Autoimmune Neuropathy through S1PR1-Dependent CD4+ T Cell Migration [AUTOIMMUNITY]
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a debilitating condition caused by autoimmune demyelination of peripheral nerves. CIDP is associated with increased IL-10, a cytokine with well-described anti-inflammatory effects. However, the role of IL-10 in CIDP is unclear. In this study, we demonstrate that IL-10 paradoxically exacerbates autoimmunity against peripheral nerves. In IL-10–deficient mice, protection from neuropathy was...
cIAP1/2-TRAF2-SHP-1-Src-MyD88 Complex Regulates Lipopolysaccharide-Induced IL-27 Production through NF-{kappa}B Activation in Human Macrophages [CLINICAL AND HUMAN IMMUNOLOGY]
The inhibitors of apoptosis (IAP) proteins, initially described in the context of apoptosis regulation as promoting cell survival, have recently emerged as key regulators of innate immune signaling. As a result, downregulation of IAP via Smac mimetics (SMM) has both survival and immunoregulatory effects. IAPs modulate cytokine production in murine models either as a single agent or in response to LPS. However, the role of SMM and the involvement...
Copper Regulates the Canonical NLRP3 Inflammasome [CLINICAL AND HUMAN IMMUNOLOGY]
Inflammasomes are multimeric protein complexes that are activated through a NOD-like receptor and regulate the proteolytic activation of caspase-1 and cytokines, like IL-1β. The NLRP3 inflammasome is implicated in many human pathologies including infections, autoinflammatory syndromes, chronic inflammation, and metabolic diseases; however, the molecular mechanisms of activation are not fully understood. In this study we show that NLRP3 inflammasome...
DDIT4 and Associated lncDDIT4 Modulate Th17 Differentiation through the DDIT4/TSC/mTOR Pathway [CLINICAL AND HUMAN IMMUNOLOGY]
Inflammation that complicates many autoimmune diseases, such as multiple sclerosis (MS), has been correlated to abnormal differentiation of Th17 cells. However, the reasons that promote Th17 cell–driven autoimmunity are yet to be discovered. In this study, we sought evidence that DNA-damage-inducible transcript 4 (DDIT4) and its associated long noncoding RNA DDIT4 (lncDDIT4) inhibit Th17 cell differentiation. We recruited 36 patients. Six MS patients...
Activation and Regulation of Blood V{delta}2 T Cells Are Amplified by TREM-1+ during Active Pulmonary Tuberculosis [IMMUNE REGULATION]
Triggering receptor expressed on myeloid cells 1 (TREM-1) is a receptor mainly expressed on myeloid cells, and it plays an important role in modulating immune response against infectious agents. The function of TREM-1 on nonmyeloid cells such as V2 T cells has not been characterized, and their role in pulmonary tuberculosis (TB) remains unclear. To assess the expression of TREM-1 on blood V2 T cells from pulmonary TB patients and investigate its...
CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin [IMMUNE REGULATION]
Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8– skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear...
CD8{alpha}+CD11c+ Extracellular Vesicles in the Lungs Control Immune Homeostasis of the Respiratory Tract via TGF-{beta}1 and IL-10 [IMMUNE REGULATION]
The immune balance of the respiratory tract is strictly regulated. Extracellular vesicles (EVs) have been reported to participate in maintaining the immune balance in the intestinal tract, but whether they are involved in regulation of the immune balance in the respiratory tract has yet to be revealed. In this study, we found that physiological EVs from lungs of WT mice (L-EVs) could be isolated, which contained the immunosuppressive cytokines TGF-β1...
Endoplasmic Reticulum-Bound Transcription Factor CREBH Stimulates RANKL-Induced Osteoclastogenesis [IMMUNE REGULATION]
Endoplasmic reticulum (ER) stress is triggered by various metabolic factors, such as cholesterol and proinflammatory cytokines. Recent studies have revealed that ER stress is closely related to skeletal disorders, such as osteoporosis. However, the precise mechanism by which ER stress regulates osteoclast differentiation has not been elucidated. In this study, we identified an ER-bound transcription factor, cAMP response element-binding protein H...
CD22 Promotes B-1b Cell Responses to T Cell-Independent Type 2 Antigens [IMMUNE REGULATION]
CD22 (Siglec-2) is a critical regulator of B cell activation and survival. CD22–/– mice generate significantly impaired Ab responses to T cell–independent type 2 (TI-2) Ags, including haptenated Ficoll and pneumococcal polysaccharides, Ags that elicit poor T cell help and activate BCR signaling via multivalent epitope crosslinking. This has been proposed to be due to impaired marginal zone (MZ) B cell development/maintenance in CD22–/– mice. However,...
MLL1 Promotes IL-7 Responsiveness and Survival during B Cell Differentiation [IMMUNE SYSTEM DEVELOPMENT]
B lymphocyte differentiation is an exquisitely regulated homeostatic process resulting in continuous production of appropriately selected B cells. Relatively small changes in gene expression can result in deregulation of this process, leading to acute lymphocytic leukemia (ALL), immune deficiency, or autoimmunity. Translocation of MLL1 (KMT2A) often results in a pro-B cell ALL, but little is known about its role in normal B cell differentiation....
Human and Rhesus Macaque KIR Haplotypes Defined by Their Transcriptomes [IMMUNOGENETICS]
The killer-cell Ig-like receptors (KIRs) play a central role in the immune recognition in infection, pregnancy, and transplantation through their interactions with MHC class I molecules. KIR genes display abundant copy number variation as well as high levels of polymorphism. As a result, it is challenging to characterize this structurally dynamic region. KIR haplotypes have been analyzed in different species using conventional characterization methods,...
Massively Parallel Sequencing of Peritoneal and Splenic B Cell Repertoires Highlights Unique Properties of B-1 Cell Antibodies [IMMUNOGENETICS]
B-1 cells are a unique subset of B cells that are positively selected for expressing autoreactive BCRs. We isolated RNA from peritoneal (B-1a, B-1b, B-2) and splenic (B-1a, marginal zone, follicular) B cells from C57BL/6 mice and used 5'-RACE to amplify the IgH V region using massively parallel sequencing. By analyzing 379,000 functional transcripts, we demonstrate that B-1a cells use a distinct and restricted repertoire. All B-1 cell subsets, especially...
Recombinant Human Vimentin Binds to P-Selectin and Blocks Neutrophil Capture and Rolling on Platelets and Endothelium [IMMUNOTHERAPY AND VACCINES]
Leukocyte adhesion to vascular endothelium and platelets is an early step in the acute inflammatory response. The initial process is mediated through P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes binding to platelets adhered to endothelium and the endothelium itself via P-selectin. Although these interactions are generally beneficial, pathologic inflammation may occur in undesirable circumstances, such as in acute lung injury (ALI) and...
Intracellular BH3 Profiling Reveals Shifts in Antiapoptotic Dependency in Human B Cell Maturation and Mitogen-Stimulated Proliferation [INFECTIOUS DISEASE AND HOST RESPONSE]
Apoptosis is critical to B cell maturation, but studies of apoptotic regulation in primary human B cells is lacking. In this study, we sought to better understand the mechanisms of apoptotic regulation in normal and activated B cells. Using intracellular BH3 profiling, we defined the Bcl2 dependency of B cell subsets from human peripheral blood and tonsillar lymphoid tissue as well as mitogen-activated B cells. We found that naive and memory B cells...
CD8+ T Cells Lack Local Signals To Produce IFN-{gamma} in the Skin during Leishmania Infection [INFECTIOUS DISEASE AND HOST RESPONSE]
Resolution of leishmaniasis depends upon parasite control and limiting inflammation. CD4+ Th1 cells are required to control parasites, whereas CD8+ T cells play a dual role: they promote Th1 cell differentiation but can also increase inflammation at the site of infection as a consequence of cytolysis. Although CD8+ T cells taken from leishmanial lesions are cytolytic, in this study, we showed that only a few CD8+ T cells produced IFN-. Correspondingly,...
CD11b+ Dendritic Cell-Mediated Anti-Mycobacterium tuberculosis Th1 Activation Is Counterregulated by CD103+ Dendritic Cells via IL-10 [INFECTIOUS DISEASE AND HOST RESPONSE]
Mycobacterium tuberculosis, the pathogen causing pulmonary tuberculosis (TB) in humans, has evolved to delay Th1 immunity in the lung. Although conventional dendritic cells (cDCs) are known to be critical to the initiation of T cell immunity, the differential roles and molecular mechanisms of migratory CD11b+ and CD103+ cDC subsets in anti–M. tuberculosis Th1 activation remain unclear. Using a murine model of pulmonary M. tuberculosis infection,...
Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1 [INFECTIOUS DISEASE AND HOST RESPONSE]
Ly6C and Sca-1 (Ly6A/E) are Ly6 family GPI-anchored surface molecules that are differentially expressed by multiple immune populations. Ly6C expression has been used to distinguish short-lived effector CD4+ T cells from memory precursor effector cells, whereas Sca-1 has been used in the identification of CD8+ memory stem cells. This study examines the expression patterns of these molecules and establishes that, in vitro, IL-27, type I IFN, and IFN-...
Antagonism of Integrin CD11b Affords Protection against Endotoxin Shock and Polymicrobial Sepsis via Attenuation of HMGB1 Nucleocytoplasmic Translocation and Extracellular Release [INNATE IMMUNITY AND INFLAMMATION]
High mobility group box 1 (HMGB1), a chromatin-binding nuclear protein, plays a critical role in sepsis by acting as a key "late-phase" inflammatory mediator. Integrin CD11b is essential for inflammatory cell activation and migration, thus mediating inflammatory responses. However, it is unclear whether CD11b participates in the development of sepsis. In this study, we report that CD11b contributes to LPS-induced endotoxin shock and microbial sepsis,...
GPR81, a Cell-Surface Receptor for Lactate, Regulates Intestinal Homeostasis and Protects Mice from Experimental Colitis [INNATE IMMUNITY AND INFLAMMATION]
At mucosal sites such as the intestine, the immune system launches robust immunity against invading pathogens while maintaining a state of tolerance to commensal flora and ingested food Ags. The molecular mechanisms underlying this phenomenon remain poorly understood. In this study, we report that signaling by GPR81, a receptor for lactate, in colonic dendritic cells and macrophages plays an important role in suppressing colonic inflammation and...
Inflammation-Sensitive Myosin-X Functionally Supports Leukocyte Extravasation by Cdc42-Mediated ICAM-1-Rich Endothelial Filopodia Formation [INNATE IMMUNITY AND INFLAMMATION]
Leukocyte transendothelial migration is key to inflammation. Leukocytes first start rolling over the inflamed endothelium, followed by firmly adhering to it. Under inflammatory conditions, endothelial cells express small finger-like protrusions that stick out into the lumen. The function and regulation of these structures are unclear. We present evidence that these ICAM-1– and F-actin–rich endothelial finger-like protrusions are filopodia and function...
Monosodium Urate Crystals Generate Nuclease-Resistant Neutrophil Extracellular Traps via a Distinct Molecular Pathway [INNATE IMMUNITY AND INFLAMMATION]
Neutrophil extracellular traps (NETs) and the cell death associated with it (NETosis) have been implicated in numerous diseases. Mechanistic studies of NETosis have typically relied on nonphysiological stimuli, such as PMA. The human disease of gout is caused by monosodium urate (MSU) crystals. We observed that DNA consistent with NETs is present in fluid from acutely inflamed joints of gout patients. NETs also coat the crystals found in uninflamed...
FOX NEWS: Woman says she was paralyzed after doing a sit-up at the gym
Woman says she was paralyzed after doing a sit-up at the gym
A fitness fanatic was left paralyzed from the neck down after falling on her head while doing an 'inverted' sit-up at the gy...
FOX NEWS: Best medicine: Woman recovering in hospital receives visit from her beloved horse
Best medicine: Woman recovering in hospital receives visit from her beloved horse
A sick woman's spirits were lifted when her fiancé arranged for a visit with their favorite hors...
FOX NEWS: Make-a-Wish grants leukemia patient her dream of having a backyard pirate ship
Make-a-Wish grants leukemia patient her dream of having a backyard pirate ship
The Make-a-Wish Foundation made a little girl's seafaring dreams come true, gifting five-year-old Leona Evans her very own backyard pirate shi...
Monday, February 19, 2018
FOX NEWS: More U.S. babies dying of suffocation, often in bed
More U.S. babies dying of suffocation, often in bed
The number of babies dying of suffocation before their first birthday has been rising in recent years, by an increase in the number of parents sharing beds with their infants, a U.S. study suggest...
FOX NEWS: Autistic boy gets birthday surprise from 'Army guys' he 'idolizes'
Autistic boy gets birthday surprise from 'Army guys' he 'idolizes'
An autistic boy got a surprise visit from the Army for his 9th birthda...
As Some Got Free Health Care, Gwen Got Squeezed: An Obamacare Dilemma
By ABBY GOODNOUGH from NYT Health http://ift.tt/2GrGW...
FOX NEWS: Tragic faces of the deadly US flu outbreak
Tragic faces of the deadly US flu outbreak
As the nation continues to fight the flu, some families are sharing their stories in hopes of preventing others from facing similar tragedie...
FOX NEWS: 2 children died from the flu over the weekend, adding to the 84 pediatric deaths this season
2 children died from the flu over the weekend, adding to the 84 pediatric deaths this season
A child from Connecticut, and New Jersey died over the weekend from flu-related illnesse...
