Immune Regulation News Volume 12.07 | Feb 28 2020

TOP STORY

Sex-Specific Adipose Tissue Imprinting of Regulatory T Cells

Researchers uncovered pronounced sexual dimorphism in T_reg cells in visceral adipose tissue (VAT). Male VAT was enriched for T_reg cells compared with female VAT, and T_reg cells from male VAT were markedly different from their female counterparts in phenotype, transcriptional landscape and chromatin accessibility. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Broad Immune Activation Underlies Shared Set Point Signatures for Vaccine Responsiveness in Healthy Individuals and Disease Activity in Patients with Lupus

Scientists uncovered baseline blood transcriptional signatures predictive of antibody responses to both influenza and yellow fever vaccinations in healthy subjects. These same signatures evaluated at clinical quiescence were correlated with disease activity in patients with systemic lupus erythematosus with plasmablast-associated flares. [Nat Med] Abstract

Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation

Investigators showed that relative to familial adenomatous polyposis, ulcerative colitis (UC) pouches reduced levels of lithocholic acid and deoxycholic acid, genes required to convert primary bile acids to secondary bile acids (SBAs), and Ruminococcaceae. In three murine colitis models, SBA supplementation reduced intestinal inflammation. [Cell Host Microbe] Abstract | Press Release | Graphical Abstract

Atypical Resistance Protein RPW8/HR Triggers Oligomerization of the NLR Immune Receptor RPP7 and Autoimmunity

In Arabidopsis thaliana, autoimmunity and cell death are linked to variants of the NLR RPP7 and the RPW8 proteins involved in broad-spectrum resistance. The authors uncovered the molecular basis for this autoimmunity and demonstrated that a homolog of RPW8, HR4^Fei-0, could trigger the assembly of a higher-order RPP7 complex, with autoimmunity signaling as a consequence. [Cell Host Microbe] Abstract | Graphical Abstract

Liver Macrophages Inhibit the Endogenous Antioxidant Response in Obesity-Associated Insulin Resistance

Researchers showed that although liver macrophages did not become proinflammatory during obesity, they displayed signs of oxidative stress. In livers of both humans and mice, antioxidant nuclear factor erythroid 2-related factor 2 was down-regulated with obesity and insulin resistance, yielding an impaired response to lipid accumulation. [Sci Transl Med] Full Article | Press Release

Caspase-11 Promotes Allergic Airway Inflammation

Scientists showed that Prostaglandin E₂ (PGE₂) inhibited caspase-11-dependent pyroptosis in murine and human macrophages. PGE₂ suppressed caspase-11 expression in murine and human macrophages and in the airways of mice with allergic inflammation. [Nat Commun] Full Article

c-FLIP Is Crucial for IL-7/IL-15-Dependent NKp46⁺ ILC Development and Protection from Intestinal Inflammation in Mice

Investigators showed that the anti-apoptotic molecule cellular FLICE-like inhibitory protein (c-FLIP) was crucial for the generation of IL-7/IL-15-dependent NKp46⁺ innate lymphoid cell (ILC)1, including conventional natural killer cells, and ILC3. [Nat Commun] Full Article

Neuronal, Stromal, and T-Regulatory Cell Crosstalk in Murine Skeletal Muscle

Researchers evidenced a striking proximity between IL-33⁺ muscle mesenchymal stromal cells (mSCs) and both large-fiber nerve bundles and small-fiber sensory neurons and demonstrated that up- or down-tuning of calcitonin-gene-related peptide signals augmentsed or diminished, respectively, IL-33 production by muscle mSCs and later accumulation of muscle Tregs. [Proc Natl Acad Sci USA] Abstract

STAT3 Signaling in Myeloid Cells Promotes Pathogenic Myelin-Specific T Cell Differentiation and Autoimmune Demyelination

Scientists report that STAT3 was activated in infiltrating monocytic cells near active multiple sclerosis lesions and that activation of STAT3 in myeloid cells was essential for leukocyte infiltration, neuroinflammation, and demyelination in experimental autoimmune encephalomyelitis. [Proc Natl Acad Sci USA] Full Article

TRAIL Receptors Serve as Stress-Associated Molecular Patterns to Promote ER-Stress-Induced Inflammation

The authors showed that ER stress initiated NF-κB activation and inflammation through transcriptional upregulation and ligand-independent activation of TRAIL receptors. ER-stress-induced TRAIL receptor activation resulted in caspase-8/FADD/RIPK1-dependent NF-κB activation and inflammatory cytokine production. [Dev Cell] Full Article | Graphical Abstract

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Plasticity of Innate Lymphoid Cell Subsets

Scientists review recent advances in research on innate lymphoid cells (ILCs), with a focus on the plasticity of these cells. They highlight the ability of ILCs to communicate with the surrounding microenvironment and discuss the possible consequences of ILC plasticity for our understanding of the biological roles of these cells. [Nat Rev Immunol] Abstract

Pathway Paradigms Revealed from the Genetics of Inflammatory Bowel Disease

The authors describe inflammatory bowel disease as a model disease in the context of leveraging human genetics to dissect interactions in cellular and molecular pathways that regulate homeostasis of the mucosal immune system. [Nature] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Takeda Acquires PvP Biologics Following Results of a Phase I Study of TAK-062 (Kuma062) for the Treatment of Celiac Disease

Takeda Pharmaceutical Company Limited announced that it has acquired PvP Biologics, Inc. following the conclusion of a Phase I proof-of-mechanism study of investigational medicine TAK-062 for the treatment of uncontrolled celiac disease. [Takeda Pharmaceutical Company Limited (Business Wire, Inc.)] Press Release

Boehringer Ingelheim Receives Positive CHMP Opinion for Nintedanib for the Treatment of Systemic Sclerosis-Associated Interstitial Lung Disease

Boehringer Ingelheim announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending granting marketing authorization for nintedanib for the treatment of systemic sclerosis-associated interstitial lung disease in adults. [Boehringer Ingelheim International GmbH] Press Release

Anokion Announces Initiation of Patient Dosing in Phase I Clinical Trial of KAN-101 in Celiac Disease

Anokion SA announced the initiation of patient dosing in the company’s multi-center Phase I clinical trial to evaluate KAN-101, the company’s lead antigen-specific drug candidate, for the treatment of celiac disease. [Anokion SA] Press Release

Takeda Receives Positive CHMP Opinion for Subcutaneous Formulation of Vedolizumab for Use as Maintenance Therapy in Adults with Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease

Takeda Pharmaceutical Company Limited announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended the approval of a subcutaneous formulation of the gut-selective biologic vedolizumab for use as maintenance therapy in adults with moderately to severely active ulcerative colitis or Crohn’s disease. [Takeda Pharmaceutical Company Limited (Business Wire, Inc.)] Press Release

Pandion Announces First Subject Dosed in a Phase I Clinical Trial of PT101, an IL-2 Mutein Fc Fusion Therapy for Autoimmune Disease

Pandion Therapeutics, Inc. announced the dosing of the first subject in a Phase I clinical trial of PT101, a novel and proprietary IL-2 mutein Fc fusion protein therapy. PT101 has shown potential to treat autoimmune diseases by expanding populations of regulatory T cells. [Pandion Therapeutics, Inc. (Business Wire, Inc.)] Press Release

Federal Judge Rules Clinical Trial Sponsors Must Publish a Decade’s Worth of Missing Data

For years, government research agencies have misinterpreted a law that requires them to collect and post clinical trial data, a federal judge ruled this week, leaving behind a ten-year gap in data that now must be made publicly available. [STAT News] Editorial

Contract Offers Unprecedented Look at Google Deal to Obtain Patient Data from the University of California

It was the fall of 2015 when researchers from Google and the University of California, San Francisco, first sat down together to hash out a research collaboration in an area that has since exploded with activity: using artificial intelligence to make predictions in the hospital. [STAT News] Editorial

NEW American Association for Cancer Research (AACR) Meeting: Evolutionary Dynamics in Carcinogenesis and Response to Therapy
March 12-15, 2020
Denver, Colorado, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Position – Leukocyte Extravasation across Postcapillary Venules (University Hospital of Muenster)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immunometabolism (Braunschweig Univesity of Technology)

Postdoctoral Investigators – Single Cell Genomics (GlaxoSmithKline plc.)

Program Manager – Research Initiatives on Neurofibromatosis (Johns Hopkins University)

Postdoctoral Fellowships – Immunology (University of Oslo)

Postdoctoral Researcher – Immunoregulation (GlaxoSmithKline plc.)

Postdoctoral Scientist – Granuloma (Texas Biomedical Research Institute)

Faculty Position – Ion Channels and Immunology (NYU School of Medicine)

Biologist – Aging (NIH National Institute on Aging)

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