from Journal of the American Society of Nephrology current issue http://ift.tt/2ljjn...
Friday, December 29, 2017
Thoughts on Turning 29
from Journal of the American Society of Nephrology current issue http://ift.tt/2lqTi...
Glomerular Disease Pathology in the Era of Proteomics: From Pattern to Pathogenesis
from Journal of the American Society of Nephrology current issue http://ift.tt/2lk51...
Renal Dendritic Cells: The Long and Winding Road
from Journal of the American Society of Nephrology current issue http://ift.tt/2lqV1...
Mesenchymal Stromal Cells for AKI after Cardiac Surgery
from Journal of the American Society of Nephrology current issue http://ift.tt/2lkt4...
Clusters Not Classifications: Making Sense of Complement-Mediated Kidney Injury
from Journal of the American Society of Nephrology current issue http://ift.tt/2lqUS...
Genetic Complexity of Autosomal Dominant Polycystic Kidney and Liver Diseases
Data indicate significant phenotypic and genotypic overlap, plus a common pathogenesis, between two groups of inherited disorders, autosomal dominant polycystic kidney diseases (ADPKD), a significant cause of ESRD, and autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD. Eight genes have been associated with ADPKD (PKD1 and PKD2), ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B), or both (GANAB). Although...
Precision Transplant Medicine: Biomarkers to the Rescue
The concept that individuals with the same disease and a similar clinical presentation may have very different outcomes and need very different therapies is not novel. With the development of many innovative tools derived from the omics technologies, transplant medicine is slowly entering the era of precision medicine. Biomarkers are the cornerstone of precision medicine, which aims to integrate biomarkers with traditional clinical information and...
Novel Insights into the Pathogenesis of Monogenic Congenital Anomalies of the Kidney and Urinary Tract
Congenital anomalies of the kidneys and urinary tract (CAKUT) comprise a large spectrum of congenital malformations ranging from severe manifestations, such as renal agenesis, to potentially milder conditions, such as vesicoureteral reflux. CAKUT causes approximately 40% of ESRD that manifests within the first three decades of life. Several lines of evidence indicate that CAKUT is often caused by recessive or dominant mutations in single (monogenic)...
DnaJ Heat Shock Protein Family B Member 9 Is a Novel Biomarker for Fibrillary GN
Fibrillary GN (FGN) is a rare primary glomerular disease. Histologic and histochemical features of FGN overlap with those of other glomerular diseases, and no unique histologic biomarkers for diagnosing FGN have been identified. We analyzed the proteomic content of glomeruli in patient biopsy specimens and detected DnaJ heat shock protein family (Hsp40) member B9 (DNAJB9) as the fourth most abundant protein in FGN glomeruli. Compared with amyloidosis...
Aldosterone Is Essential for Angiotensin II-Induced Upregulation of Pendrin
The renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, increasing levels of the Cl–/HCO3– exchanger pendrin in β-intercalated cells and the Na+-Cl– cotransporter (NCC) in distal convoluted tubules. However, the independent roles of AngII and aldosterone in regulating these levels...
Cardiovascular Effects of Renal Distal Tubule Deletion of the FGF Receptor 1 Gene
The bone-derived hormone fibroblast growth factor–23 (FGF-23) activates complexes composed of FGF receptors (FGFRs), including FGFR1, and α-Klotho in the kidney distal tubule (DT), leading to increased sodium retention and hypertension. However, the role of FGFR1 in regulating renal processes linked to hypertension is unclear. Here, we investigated the effects of selective FGFR1 loss in the DT. Conditional knockout (cKO) of FGFR1 in the DT (FGFR1DT-cKO...
Kidney Proximal Tubule Lipoapoptosis Is Regulated by Fatty Acid Transporter-2 (FATP2)
Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across the damaged glomerular filtration barrier and subsequent reabsorption by the downstream proximal tubule, causing lipoapoptosis. We sought to identify the apical proximal tubule transporter that mediates NEFA uptake and cytotoxicity. We observed transporter-mediated...
ShcA Adaptor Protein Promotes Nephrin Endocytosis and Is Upregulated in Proteinuric Nephropathies
Nephrin is a key structural component of the podocyte slit diaphragm, and proper expression of nephrin on the cell surface is critical to ensure integrity of the blood filtration barrier. Maintenance of nephrin within this unique cell junction has been proposed to require dynamic phosphorylation events and endocytic recycling, although the molecular mechanisms that control this interplay are poorly understood. Here, we investigated the possibility...
Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the Kidney
Preconditioning with a low dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response generated by preconditioning remains unknown. Here, using the kidney as a model organ, we investigated cell type–specific responses to preconditioning....
FXR/TGR5 Dual Agonist Prevents Progression of Nephropathy in Diabetes and Obesity
Bile acids are ligands for the nuclear hormone receptor farnesoid X receptor (FXR) and the G protein–coupled receptor TGR5. We have shown that FXR and TGR5 have renoprotective roles in diabetes- and obesity-related kidney disease. Here, we determined whether these effects are mediated through differential or synergistic signaling pathways. We administered the FXR/TGR5 dual agonist INT-767 to DBA/2J mice with streptozotocin-induced diabetes, db/db...
Opposing Roles of Dendritic Cell Subsets in Experimental GN
Dendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, to perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that are not unique to DCs. Here, we evaluated the role of DCs in renal inflammation using a CD11c reporter mouse line and two mouse lines with DC-specific reporters, Zbtb46-GFP and Snx22-GFP. Multiphoton...
MYH9 E1841K Mutation Augments Proteinuria and Podocyte Injury and Migration
Intronic variants of the MYH9 gene that encodes the nonmuscle myosin heavy chain IIA are associated with diabetic nephropathy in European Americans and with sickle cell disease–associated nephropathy. However, the causal functional variants of MYH9 have remained elusive. Rare missense mutations in MYH9 cause macrothrombocytopenia and are occasionally associated with development of nephropathy. The E1841K mutation is among the common MYH9 missense...
Collectin-11 Promotes the Development of Renal Tubulointerstitial Fibrosis
Collectin-11 is a recently described soluble C-type lectin, a pattern recognition molecule of the innate immune system that has distinct roles in host defense, embryonic development, and acute inflammation. However, little is known regarding the role of collectin-11 in tissue fibrosis. Here, we investigated collectin-11 in the context of renal ischemia-reperfusion injury. Compared with wild-type littermate controls, Collec11 deficient (CL-11–/–)...
Wnt/{beta}-Catenin-Promoted Macrophage Alternative Activation Contributes to Kidney Fibrosis
The Wnt/β-catenin pathway is crucial in normal development and throughout life, but aberrant activation of this pathway has been linked to kidney fibrosis, although the mechanisms involved remain incompletely determined. Here, we investigated the role of Wnt/β-catenin in regulating macrophage activation and the contribution thereof to kidney fibrosis. Treatment of macrophages with Wnt3a exacerbated IL-4– or TGFβ1-induced macrophage alternative (M2)...
Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI
The proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule–specific deletion of Drp1 prevented the renal ischemia-reperfusion–induced...
Incident CKD after Radical or Partial Nephrectomy
The comparative effectiveness of partial nephrectomy versus radical nephrectomy to preserve kidney function has not been well established. We determined the risk of clinically significant (stage 4 and higher) CKD after radical or partial nephrectomy among veterans treated for kidney cancer in the Veterans Health Administration (2001–2013). Among patients with preoperative eGFR≥30 ml/min per 1.73 m2, the incidence of CKD stage 4 or higher after radical...
Particulate Matter Air Pollution and the Risk of Incident CKD and Progression to ESRD
Elevated levels of fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5) are associated with increased risk of cardiovascular outcomes and death, but their association with risk of CKD and ESRD is unknown. We linked the Environmental Protection Agency and the Department of Veterans Affairs databases to build an observational cohort of 2,482,737 United States veterans, and used survival models to evaluate the association of PM2.5 concentrations...
DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN
Fibrillary GN is a rare form of GN of uncertain pathogenesis that is characterized by the glomerular accumulation of randomly arranged, nonbranching fibrils (12–24 nm) composed of Ig and complement proteins. In this study, we used mass spectrometry to comprehensively define the glomerular proteome in fibrillary GN compared with that in controls and nonfibrillary GN renal diseases. We isolated glomeruli from formalin-fixed and paraffin-embedded biopsy...
Factor H Competitor Generated by Gene Conversion Events Associates with Atypical Hemolytic Uremic Syndrome
Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy caused by complement pathogenic variants, mainly affects the kidney microvasculature. A retrospective genetic analysis in our aHUS cohort (n=513) using multiple ligation probe amplification uncovered nine unrelated patients carrying a genetic abnormality in the complement factor H related 1 gene (CFHR1) that originates by recurrent gene conversion events between...
Metabolic Effects of Diet and Exercise in Patients with Moderate to Severe CKD: A Randomized Clinical Trial
CKD is steadily increasing along with obesity worldwide. Furthermore, obesity is a proinflammatory risk factor for progression of CKD and cardiovascular disease. We tested the hypothesis that implementation of caloric restriction and aerobic exercise is feasible and can improve the proinflammatory metabolic milieu in patients with moderate to severe CKD through a pilot, randomized, 2x2 factorial design trial. Of 122 participants consented, 111 were...
Allogeneic Mesenchymal Stem Cells for Treatment of AKI after Cardiac Surgery
AKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after...
Complement Activation in Peritoneal Dialysis-Induced Arteriolopathy
Cardiovascular disease (CVD) is the leading cause of increased mortality in patients with CKD and is further aggravated by peritoneal dialysis (PD). Children are devoid of preexisting CVD and provide unique insight into specific uremia- and PD-induced pathomechanisms of CVD. We obtained peritoneal specimens from children with stage 5 CKD at time of PD catheter insertion (CKD5 group), children with established PD (PD group), and age-matched nonuremic...
Cluster Analysis Identifies Distinct Pathogenetic Patterns in C3 Glomerulopathies/Immune Complex-Mediated Membranoproliferative GN
Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement–mediated C3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a...
Impaired {beta}-Oxidation and Altered Complex Lipid Fatty Acid Partitioning with Advancing CKD
Studies of lipids in CKD, including ESRD, have been limited to measures of conventional lipid profiles. We aimed to systematically identify 17 different lipid classes and associate the abundance thereof with alterations in acylcarnitines, a metric of β-oxidation, across stages of CKD. From the Clinical Phenotyping Resource and Biobank Core (CPROBE) cohort of 1235 adults, we selected a panel of 214 participants: 36 with stage 1 or 2 CKD, 99 with stage...
FOX NEWS: Flu outbreak already reported in 36 states, CDC says
Flu outbreak already reported in 36 states, CDC says
The early start of the outbreaks, which usually see a peak in February, has to do with the low efficacy of the vaccine and possibly the cold temperatures gripping much of the countr...
FOX NEWS: Woman sues hospital over nude photo taken of her on operating table
Woman sues hospital over nude photo taken of her on operating table
A woman has sued the Pennsylvania hospital where she once worked over nude photos taken of her while she was on the operating tabl...
FOX NEWS: Frostbite: Know the signs and symptoms
Frostbite: Know the signs and symptoms
When old man winter comes to town, it's important to make sure you and your family are ready for more than just a heavy snow fal...
FOX NEWS: Cashier, butcher help deliver baby at California market
Cashier, butcher help deliver baby at California market
“So many emotions in one," said the store owner. "I’m still in shock yet very happy...
FOX NEWS: OB-GYN delivers patient's twins 14 hours after giving birth to her own daughter
OB-GYN delivers patient's twins 14 hours after giving birth to her own daughter
An OB-GYN who was determined not to miss the birth of her patient’s twins swooped in to deliver the two babies just 14 hours after she gave birth hersel...
Thursday, December 28, 2017
FOX NEWS: Family praises 'miracle surgeon' after daughter's emergency surgery
Family praises 'miracle surgeon' after daughter's emergency surgery
The family of a 4-year-old brain tumor patient are praising the “miracle surgeon” who unexpectedly gave them hope after their daughter’s operation, Fox 35 reporte...
Do Australians Need a Sugar Intervention?
By KASSIE BRACKEN, JONAH M. KESSEL and TAIGE JENSEN from NYT Health http://ift.tt/2CiWV...
FOX NEWS: WHO considers adding 'gaming disorder' to list of mental diseases
WHO considers adding 'gaming disorder' to list of mental diseases
The WHO guidelines are the international standard for reporting health condition...
Wednesday, December 27, 2017
F.D.A. Leaves Tainted Foods on Shelves Too Long, Report Finds
By SHEILA KAPLAN from NYT Health http://ift.tt/2Cfau...
FOX NEWS: China clones first gene-edited dog, sentencing him to possible early death
China clones first gene-edited dog, sentencing him to possible early death
The dog's genome was edited so it would develop atherosclerosis and scientists could further advance the battle against the disease in human...
FOX NEWS: China clones first gene-edited dog, but it's sentenced to die of heart disease
China clones first gene-edited dog, but it's sentenced to die of heart disease
The dog's genome was edited so it would develop atherosclerosis and scientists could further advance the battle against the disease in human...
FOX NEWS: Marijuana use increases among pregnant women in California, study says
Marijuana use increases among pregnant women in California, study says
A study by scientists in Northern California found smoking marijuana is on the rise among pregnant women in the U....
Tuesday, December 26, 2017
Measles Deaths Fall to a Record Low Worldwide
By DONALD G. McNEIL Jr. from NYT Health http://ift.tt/2BSwF...
Monday, December 25, 2017
One Man’s Stand Against Junk Food as Diabetes Climbs Across India
By GEETA ANAND from NYT Health http://ift.tt/2BBxR...
Sunday, December 24, 2017
FOX NEWS: American expat fights for his life after falling off roof in Bali while chasing monkey who stole his Pittsburgh Steelers cap
American expat fights for his life after falling off roof in Bali while chasing monkey who stole his Pittsburgh Steelers cap
A Florida man living in Indonesia is fighting for his life after he plunged 33 feet off a rooftop while chasing a monkey that had snatched his favorite Pittsburgh Steelers ca...
Saturday, December 23, 2017
FOX NEWS: Utah dad prepared to take out loan after porch pirates steal pricey meds from ill son
Utah dad prepared to take out loan after porch pirates steal pricey meds from ill son
A single father from Riverdale, Utah, was prepared to take out a loan after porch pirates stole $5K worth of medication his sick son desperately need...
In Asia’s Fattest Country, Nutritionists Take Money From Food Giants
By THOMAS FULLER, ANAHAD O’CONNOR and MATT RICHTEL from NYT Health http://ift.tt/2l0UL...
Friday, December 22, 2017
FOX NEWS: 86-year-old woman with dementia warms up to Santa ─ and makes him cry
86-year-old woman with dementia warms up to Santa ─ and makes him cry
Karen Rangel was diagnosed with Alzheimer’s in 2014 and was recently put on hospice car...
FOX NEWS: War Horses for Veterans helps returning soldiers in innovative way
War Horses for Veterans helps returning soldiers in innovative way
War Horses for Veterans offers a three-day equine and networking experience where they bond with horses, as well as each othe...
FOX NEWS: Eating fish weekly raises IQ by almost 5 points in children, study finds
Eating fish weekly raises IQ by almost 5 points in children, study finds
The study was conducted last month among 541 Chinese children between the ages of 9 and 1...
Greater Access to Donated Livers Promised to Transplant Patients
By TED ALCORN from NYT Health http://ift.tt/2Byxz...
Thursday, December 21, 2017
FOX NEWS: Could ‘Christmas tree syndrome’ ruin your holidays?
Could ‘Christmas tree syndrome’ ruin your holidays?
Could "Christmas tree syndrome” wreak havoc on your holidays? Inside the holiday health risk that could make you sic...
FOX NEWS: Why ‘bad’ foods aren't really bad for you
Why ‘bad’ foods aren't really bad for you
Nutritional studies can be confusing. One week coffee is good for you, and the next week it’s bad for you. Fox News’ Dr. Manny Alvarez sits down with Dr. Aaron Carroll, author of "The Bad Food Bible” to discuss which controversial foods aren’t really bad for you after al...
FOX NEWS: Could early retirement shorten your life?
Could early retirement shorten your life?
A new study from Cornell University finds that people who call it quits at 62 and start collecting Social Security don't live as long as those who wai...
FOX NEWS: Dr. Siegel offers insight on treating Amtrak crash victims
Dr. Siegel offers insight on treating Amtrak crash victims
The Fox News Medial A-Team member details the types of injuries caused by a derailment and the needs of local hospital...
FOX NEWS: Experts warn cold, flu season will peak Christmas week
Experts warn cold, flu season will peak Christmas week
The regions that could be hit the hardest are mid-Atlantic states and the southern half of the countr...
FOX NEWS: US life expectancy decreases for second straight year as overdose deaths soar
US life expectancy decreases for second straight year as overdose deaths soar
U.S. deaths from drug overdoses skyrocketed 21 percent last year, and for the second straight year dragged down how long Americans are expected to liv...
FOX NEWS: Woman says she is her own twin sister due to rare genetic condition
Woman says she is her own twin sister due to rare genetic condition
Muhl, a singer and entertainer from California, has been diagnosed with rare genetic condition called chimeris...
Wednesday, December 20, 2017
FOX NEWS: Michigan cities, counties' opioid lawsuit targets drug companies, pharmacies
Michigan cities, counties' opioid lawsuit targets drug companies, pharmacies
Nine cities and counties in Michigan have filed a lawsuit against 21 drug companies, distributors and pharmacies, accusing them of helping fuel the national opioid epidemic -- and costing taxpayers mone...
Tuesday, December 19, 2017
E.P.A. Delays Bans on Uses of Hazardous Chemicals
By SHEILA KAPLAN from NYT Health http://ift.tt/2D70s...
FOX NEWS: Tennessee woman gives birth to baby who was frozen as embryo for 24 years
Tennessee woman gives birth to baby who was frozen as embryo for 24 years
A Tennessee woman gave birth to Emma, a baby who was frozen in an embryo for 24 year...
A Federal Ban on Making Lethal Viruses Is Lifted
By DONALD G. McNEIL Jr. from NYT Health http://ift.tt/2oK6W...
Monday, December 18, 2017
A Beginners Guide to Analyzing and Visualizing Mass Cytometry Data [IMMUNOLOGY NOTES AND RESOURCES]
Mass cytometry has revolutionized the study of cellular and phenotypic diversity, significantly expanding the number of phenotypic and functional characteristics that can be measured at the single-cell level. This high-dimensional analysis platform has necessitated the development of new data analysis approaches. Many of these algorithms circumvent traditional approaches used in flow cytometric analysis, fundamentally changing the way these data...
The Reign of Antibodies: A Celebration of and Tribute to Michael Potter and His Homogeneous Immunoglobulin Workshops [PILLARS OF IMMUNOLOGY]
from The Journal of Immunology current issue http://ift.tt/2Baxs...
Pillars Article: Evidence for Amino Acid Sequence Differences among Proteins Resembling the L-chain Subunits of Immunoglobulins. J. Mol. Biol. 1965. 12: 81-87 [PILLARS OF IMMUNOLOGY]
from The Journal of Immunology current issue http://ift.tt/2yUt8...
Salmonella Vaccines: Conduits for Protective Antigens [BRIEF REVIEWS]
Vaccines afford a better and more cost-effective approach to combatting infectious diseases than continued reliance on antibiotics or antiviral or antiparasite drugs in the current era of increasing incidences of diseases caused by drug-resistant pathogens. Recombinant attenuated Salmonella vaccines (RASVs) have been significantly improved to exhibit the same or better attributes than wild-type parental strains to colonize internal lymphoid tissues...
The Role of MHC-E in T Cell Immunity Is Conserved among Humans, Rhesus Macaques, and Cynomolgus Macaques [ANTIGEN RECOGNITION AND RESPONSES]
MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8+ T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development...
Superoxide Production by NADPH Oxidase Intensifies Macrophage Antiviral Responses during Diabetogenic Coxsackievirus Infection [AUTOIMMUNITY]
Coxsackievirus B infections are suspected environmental triggers of type 1 diabetes (T1D) and macrophage antiviral responses may provide a link to virus-induced T1D. We previously demonstrated an important role for NADPH oxidase (NOX)–derived superoxide production during T1D pathogenesis, as NOX-deficient NOD mice (NOD.Ncf1m1J) were protected against T1D due, in part, to impaired proinflammatory TLR signaling in NOD.Ncf1m1J macrophages. Therefore,...
Essential Role of CARD14 in Murine Experimental Psoriasis [AUTOIMMUNITY]
Caspase recruitment domain family member 14 (CARD14) was recently identified as a psoriasis-susceptibility gene, but its immunological role in the pathogenesis of psoriasis in vivo remains unclear. In this study, we examined the role of CARD14 in murine experimental models of psoriasis induced by either imiquimod (IMQ) cream or recombinant IL-23 injection. In all models tested, the psoriasiform skin inflammation was abrogated in Card14–/– mice. Comparison...
The Loss of TET2 Promotes CD8+ T Cell Memory Differentiation [IMMUNE REGULATION]
T cell differentiation requires appropriate regulation of DNA methylation. In this article, we demonstrate that the methylcytosine dioxygenase ten-eleven translocation (TET)2 regulates CD8+ T cell differentiation. In a murine model of acute viral infection, TET2 loss promotes early acquisition of a memory CD8+ T cell fate in a cell-intrinsic manner without disrupting Ag-driven cell expansion or effector function. Upon secondary recall, TET2-deficient...
Downregulation of NFAT3 Due to Lack of T-Box Transcription Factor TBX5 Is Crucial for Cytokine Expression in T Cells [IMMUNE REGULATION]
The NFAT family transcription factors play crucial roles in immunological and other biological activities. NFAT3 is rarely expressed in T cells, and the mechanisms and significance of the specific NFAT3 downregulation in T cells have been unknown. In human CD4+ T cells, overexpression of NFAT1 and NFAT3 enhanced and suppressed IL-2 expression, respectively. NFAT3 downregulation in Jurkat cells using RNA interference technology augmented IL-2 expression,...
Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance [IMMUNE REGULATION]
It has been shown that dominant tolerance, namely in transplantation, requires Foxp3+ regulatory T cells. Although most tolerance-inducing regimens rely on regulatory T cells, we found that induction of tolerance to proteins in aluminum hydroxide can be achieved in Foxp3-deficient mice using nondepleting anti-CD4 Abs. This type of tolerance is Ag specific, and tolerant mice retain immune competence to respond to unrelated Ags. We demonstrated with...
STAT5B: A Differential Regulator of the Life and Death of CD4+ Effector Memory T Cells [IMMUNE REGULATION]
Understanding the control of Ag restimulation-induced T cell death (RICD), especially in cancer immunotherapy, where highly proliferating T cells will encounter potentially large amounts of tumor Ags, is important now more than ever. It has been known that growth cytokines make T cells susceptible to RICD, but the precise molecular mediators that govern this in T cell subsets is unknown until now. STAT proteins are a family of transcription factors...
Ultraviolet B-Induced Maturation of CD11b-Type Langerin- Dendritic Cells Controls the Expansion of Foxp3+ Regulatory T Cells in the Skin [IMMUNE REGULATION]
Skin dendritic cells (DCs) are divided into several subsets with distinctive functions. This study shows a previously unappreciated role of dermal CD11b-type Langerin– DCs in maintaining immunological self-tolerance after UVB exposure. After UVB exposure, dermal CD11b-type Langerin– DCs upregulated surface CD86 expression, induced proliferation of Foxp3+ regulatory T (Treg) cells without exogenous Ags, and upregulated a set of genes associated with...
The Role of Macrophages in the Response to TNF Inhibition in Experimental Arthritis [IMMUNE SYSTEM DEVELOPMENT]
The reduction of synovial tissue macrophages is a reliable biomarker for clinical improvement in patients with rheumatoid arthritis (RA), and macrophages are reduced in synovial tissue shortly after initiation of TNF inhibitors. The mechanism for this initial response is unclear. These studies were performed to identify the mechanisms responsible for the initial reduction of macrophages following TNF inhibition, positing that efflux to draining lymph...
CXCR3/CXCL10 Axis Shapes Tissue Distribution of Memory Phenotype CD8+ T Cells in Nonimmunized Mice [IMMUNE SYSTEM DEVELOPMENT]
The preimmune repertoire consists of mature T lymphocytes that have not yet been stimulated in the periphery. Memory phenotype (MP) cells have been reported as part of the preimmune repertoire (i.e., T cells bearing memory markers despite lack of engagement with cognate Ag); however, little is known about their trafficking and function. In this study, we hypothesized that MP cells, naive to TCR stimulation, constitute a transient population that...
A Novel Pkhd1 Mutation Interacts with the Nonobese Diabetic Genetic Background To Cause Autoimmune Cholangitis [IMMUNOGENETICS]
We previously reported that NOD.c3c4 mice develop spontaneous autoimmune biliary disease (ABD) with anti-mitochondrial Abs, histopathological lesions, and autoimmune T lymphocytes similar to human primary biliary cholangitis. In this article, we demonstrate that ABD in NOD.c3c4 and related NOD ABD strains is caused by a chromosome 1 region that includes a novel mutation in polycystic kidney and hepatic disease 1 (Pkhd1). We show that a long terminal...
Live Attenuated Leishmania donovani Centrin Gene-Deleted Parasites Induce IL-23-Dependent IL-17-Protective Immune Response against Visceral Leishmaniasis in a Murine Model [IMMUNOTHERAPY AND VACCINES]
No vaccine exists against visceral leishmaniasis. To develop effective vaccines, we have previously reported protective role of live attenuated centrin gene–deleted Leishmania donovani (LdCen–/–) parasites through induction of Th1 type immune response in mice, hamsters, and dogs. In this study, we specifically explored the role of Th17 cells in LdCen–/–-induced host protection in mice. Our results showed that compared with wild-type L. donovani infection,...
Amplifying IFN-{gamma} Signaling in Dendritic Cells by CD11c-Specific Loss of SOCS1 Increases Innate Immunity to Infection while Decreasing Adaptive Immunity [INFECTIOUS DISEASE AND HOST RESPONSE]
Although prophylactic vaccines provide protective humoral immunity against infectious agents, vaccines that elicit potent CD8 T cell responses are valuable tools to shape and drive cellular immunity against cancer and intracellular infection. In particular, IFN-–polarized cytotoxic CD8 T cell immunity is considered optimal for protective immunity against intracellular Ags. Suppressor of cytokine signaling (SOCS)1 is a cross-functional negative regulator...
Toxoplasma gondii Inactivates Human Plasmacytoid Dendritic Cells by Functional Mimicry of IL-10 [INFECTIOUS DISEASE AND HOST RESPONSE]
Plasmacytoid dendritic cells (pDCs) are the major producers of IFN-α, an antiviral cytokine involved in immunomodulation and control of HIV type 1 replication, whereas Toxoplasma gondii is a life-threatening opportunistic infection in AIDS patients. During infection with HIV type 1, human pDCs decrease in circulation and remaining pDC produce lower amounts of IFN-α in response to viral stimulation. In this study, we investigated the impact of coinfection...
NOX2-Derived Reactive Oxygen Species Control Inflammation during Leishmania amazonensis Infection by Mediating Infection-Induced Neutrophil Apoptosis [INFECTIOUS DISEASE AND HOST RESPONSE]
Reactive oxygen species (ROS) produced by NADPH phagocyte oxidase isoform (NOX2) are critical for the elimination of intracellular pathogens in many infections. Despite their importance, the role of ROS following infection with the eukaryotic pathogen Leishmania has not been fully elucidated. We addressed the role of ROS in C57BL/6 mice following intradermal infection with Leishmania amazonensis. Despite equivalent parasite loads compared with wild-type...
The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression Kinetics with Atypical RNASEL Induction [INFECTIOUS DISEASE AND HOST RESPONSE]
Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity are unknown, but they may be linked to unique immunological features that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to viral infection by inducing IFNs, which trigger antiviral defenses through IFN-stimulated gene (ISG) expression. Although the IFN system...
IL-1{beta} Induces Pathologically Activated Osteoclasts Bearing Extremely High Levels of Resorbing Activity: A Possible Pathological Subpopulation of Osteoclasts, Accompanied by Suppressed Expression of Kindlin-3 and Talin-1 [INNATE IMMUNITY AND INFLAMMATION]
As osteoclasts have the central roles in normal bone remodeling, it is ideal to regulate only the osteoclasts performing pathological bone destruction without affecting normal osteoclasts. Based on a hypothesis that pathological osteoclasts form under the pathological microenvironment of the bone tissues, we here set up optimum culture conditions to examine the entity of pathologically activated osteoclasts (PAOCs). Through searching various inflammatory...
IL-33-Responsive Group 2 Innate Lymphoid Cells Are Regulated by Female Sex Hormones in the Uterus [INNATE IMMUNITY AND INFLAMMATION]
Group 2 innate lymphoid cells (ILC2s) reside in multiple organs in the body, where they play roles in immunity, tissue homeostasis, and metabolic regulation. However, little is known about the regulatory mechanisms of ILC2s in different organs. Here, we identified ILC2s in the mouse uterus and found that they express cell surface molecules, including the IL-33 receptor, ST2, that are roughly comparable to those expressed by lung ILC2s. Both in vivo...
Identification of IFN-{gamma} and IL-27 as Critical Regulators of Respiratory Syncytial Virus-Induced Exacerbation of Allergic Airways Disease in a Mouse Model [INNATE IMMUNITY AND INFLAMMATION]
Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exacerbations are the main cause of morbidity and mortality associated with asthma, and significantly contribute to asthma-associated healthcare costs. Although glucocorticoids are used to manage exacerbations, some patients respond to them poorly. The underlying mechanisms...
The Activation of Human Dermal Microvascular Cells by Poly(I:C), Lipopolysaccharide, Imiquimod, and ODN2395 Is Mediated by the Fli1/FOXO3A Pathway [INNATE IMMUNITY AND INFLAMMATION]
Endothelial cell (EC) dysfunction has been associated with inflammatory and autoimmune diseases; however, the factors contributing to this dysfunction have not been fully explored. Because activation of TLRs has been implicated in autoimmune diseases, the goal of this study was to determine the effects of TLR ligands on EC function. Human dermal microvascular ECs (HDMECs) treated with TLR3 [Poly(I:C)], TLR4 (LPS), and TLR7 (imiquimod) agonists showed...
Reticulon-1 and Reduced Migration toward Chemoattractants by Macrophages Differentiated from the Bone Marrow of Ultraviolet-Irradiated and Ultraviolet-Chimeric Mice [INNATE IMMUNITY AND INFLAMMATION]
The ability of macrophages to respond to chemoattractants and inflammatory signals is important for their migration to sites of inflammation and immune activity and for host responses to infection. Macrophages differentiated from the bone marrow (BM) of UV-irradiated mice, even after activation with LPS, migrated inefficiently toward CSF-1 and CCL2. When BM cells were harvested from UV-irradiated mice and transplanted into naive mice, the recipient...
Embryonic Lethality and Host Immunity of RelA-Deficient Mice Are Mediated by Both Apoptosis and Necroptosis [INNATE IMMUNITY AND INFLAMMATION]
In mammalian cells, signaling pathways triggered by TNF can be switched from NF-B activation to apoptosis and/or necroptosis. The in vivo mechanisms underlying the mutual regulation of these three signaling pathways are poorly understood. In this article, we report that the embryonic lethality of RelA-deficient mice is partially prevented by the deletion of Rip3 or Mlkl, but it is fully rescued by the combined ablation of Fadd and Rip3 or Mlkl or...
Rhesus Macaque Myeloid-Derived Suppressor Cells Demonstrate T Cell Inhibitory Functions and Are Transiently Increased after Vaccination [INNATE IMMUNITY AND INFLAMMATION]
Myeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses in several pathological conditions. Whether MDSCs increase and influence T cell responses in temporary inflammation, such as after vaccine administration, is unknown. Using the rhesus macaque model, which is critical for late-stage vaccine testing, we demonstrate that monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs can be detected using several of the markers...
Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging [INNATE IMMUNITY AND INFLAMMATION]
Dysregulated inflammation is implicated in the pathobiology of aging, yet platelet–leukocyte interactions and downstream cytokine synthesis in aging remains poorly understood. Platelets and monocytes were isolated from healthy younger (age <45, n = 37) and older (age ≥65, n = 30) adults and incubated together under autologous and nonautologous conditions. Synthesis of inflammatory cytokines by monocytes, alone or in the presence of platelets,...
NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes [INNATE IMMUNITY AND INFLAMMATION]
Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and...
Hospital Giants Vie for Patients in Effort to Fend Off New Rivals
By REED ABELSON from NYT Health http://ift.tt/2B9vK...
FOX NEWS: Woman develops rare c-section scar condition 5 times
Woman develops rare c-section scar condition 5 times
In a rare occurrence, a pregnant woman's gestational sac — the small vessel that holds the developing embryo — attached not to the lining of her womb but instead to a scar left over from a previous C-sectio...
FOX NEWS: Seasonal affective disorder: It's more than the winter blues
Seasonal affective disorder: It's more than the winter blues
Why are you feeling so bla...
FOX NEWS: 7 harmful houseplants that are a danger in disguise
7 harmful houseplants that are a danger in disguise
You might like to brighten up your home office or window sills with colorful flowers and hardy, inspiring greener...
FOX NEWS: Pediatrician meets teen organ donor's family in emotional union
Pediatrician meets teen organ donor's family in emotional union
A Texas pediatrician connected with a grieving grandmother on Sunday to celebrate the 15-year-old teen who saved her life through organ donatio...
FOX NEWS: Opioid epidemic burdening grandparents, foster care
Opioid epidemic burdening grandparents, foster care
As the opioid epidemic pushes children out of their parents’ custody, grandparents and other relatives are forced to step u...
FOX NEWS: US health officials to target high-risk alternative remedies
US health officials to target high-risk alternative remedies
U.S. health officials plan to crack down on a growing number of unproven alternative remedies, focusing on those containing dangerous ingredients that have occasionally been linked to serious injury and deat...
FOX NEWS: Bears' Zach Miller shares video of first steps following gruesome leg injury
Bears' Zach Miller shares video of first steps following gruesome leg injury
Chicago Bears tight end Zach Miller posted a 17-second video to Instagram on Sunday that showed him slowly taking steps without the assistance of crutches, just weeks after he underwent emergency surgery to repair a torn artery that could have cost him his le...
FOX NEWS: 5 warning signs your appendix might burst
5 warning signs your appendix might burst
These symptoms may warrant a call to your doctor or a trip to the emergency roo...
FOX NEWS: Company recalls salami, prosciutto over possible salmonella contamination
Company recalls salami, prosciutto over possible salmonella contamination
A Canadian-based manufacturer is recalling ready-to-eat salami and speck products that are sold and distributed in the U.S. over concerns of possible salmonella contaminatio...
Sunday, December 17, 2017
Drug Company Under Fire After Revealing Dengue Vaccine May Harm Some
By DENISE GRADY and KATIE THOMAS from NYT Health http://ift.tt/2AM16...
Saturday, December 16, 2017
In Opioid Battle, Cherokee Want Their Day in Tribal Court
By JAN HOFFMAN from NYT Health http://ift.tt/2AZiG...
Uproar Over Purported Ban at C.D.C. of Words Like ‘Fetus’
By SHEILA KAPLAN and DONALD G. McNEIL Jr. from NYT Health http://ift.tt/2kAH5...
Friday, December 15, 2017
Six Lessons in Helping African Women Avoid H.I.V.
By DONALD G. McNEIL Jr. from NYT Health http://ift.tt/2oiUl...
A Last Push for Obamacare Sign-ups — and Worries About Who Got Hurt
By KATE ZERNIKE and ROBERT PEAR from NYT Health http://ift.tt/2Cj7z...
FOX NEWS: Mom of 5 who lost home in Hurricane Harvey learns she's expecting quadruplets
Mom of 5 who lost home in Hurricane Harvey learns she's expecting quadruplets
A Hurricane Harvey survivor who lost her home in the devastating floodwaters was shocked to learn that she is expecting naturally conceived quadruplet...
FOX NEWS: Mom claims Hatchimals bath bomb gave daughter chemical burns
Mom claims Hatchimals bath bomb gave daughter chemical burns
A mother is sounding the alarm over one of the season’s hottest toys after she claims it left her daughter with chemical burn...
