Immune Regulation News Volume 9.44 | Nov 17 2017

TOP STORY

Gut Bacteria Are Sensitive to Salt

Common salt reduced the number of certain lactic acid bacteria in the gut of mice and humans according to a study by Berlin’s Max Delbrück Center and Charité. This had an impact on immune cells, which are partly responsible for autoimmune diseases and hypertension. Probiotics ameliorated the symptoms of disease in mice. [Press release from Max Delbrück Center for Molecular Medicine discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression

Deletion analyses of the two key hypoxia-inducible transcription factor (HIF) isoforms found that HIF-1α, but not HIF-2α, was essential for the effector state in CD8⁺ T cells. Furthermore, loss of HIF-1α in CD8⁺ T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization. [Cancer Cell] Full Article | Press Release

Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-Priming Anti-Viral CD4⁺ T Cell Immunity

The TNF receptor superfamily member GITR is important for CD4⁺ T cell accumulation and control of chronic lymphocytic choriomeningitis virus. The authors found that type I interferon induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived antigen-presenting cells and CD80 and CD86 predominantly on classical dendritic cells. [Immunity] Abstract | Graphical Abstract

Targeting Interleukin-1β Protects from Aortic Aneurysms Induced by Disrupted Transforming Growth Factor β Signaling

Investigators report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of transforming growth factor β . The results revealed that Smad4 inhibition activated IL-1β in SMCs. [Immunity] Abstract | Graphical Abstract

Apoptosis in Mesenchymal Stromal Cells Induces In Vivo Recipient-Mediated Immunomodulation

Using a murine model of graft-versus-host disease, the authors demonstrated that mesenchymal stromal cells (MSCs) are actively induced to undergo perforin-dependent apoptosis by recipient cytotoxic cells and that this process is essential to initiate MSC-induced immunosuppression. [Sci Transl Med] Abstract

Wiskott–Aldrich Syndrome Protein Regulates Autophagy and Inflammasome Activity in Innate Immune Cells

Scientists showed that deficiency of Wiskott–Aldrich syndrome (WAS) protein, which signals to the actin cytoskeleton, modulates autophagy and inflammasome function. In a model of sterile inflammation utilizing TLR4 ligation followed by ATP or nigericin treatment, inflammasome activation was enhanced in monocytes from WAS patients and in WAS-knockout mouse dendritic cells. [Nat Commun] Full Article

Loss of HIF-1α in Natural Killer Cells Inhibits Tumor Growth by Stimulating Non-Productive Angiogenesis

Researchers found that deletion of hypoxia-inducible factor (HIF)-1α in natural killer cells inhibited tumor growth despite impaired tumor cell killing. Tumors developing in these conditions were characterized by a high-density network of immature vessels, severe hemorrhage, increased hypoxia, and facilitated metastasis due to non-productive angiogenesis. [Nat Commun] Full Article

SIRPα⁺ Dendritic Cells Regulate Homeostasis of Fibroblastic Reticular Cells via TNF Receptor Ligands in the Adult Spleen

The authors showed that ablation of either signal regulatory protein α (SIRPα), an Ig superfamily protein, or its ligand CD47 in conventional dendritic cells (cDCs) markedly reduced the number of CD4⁺ cDCs as well as that of Pdpn⁺ fibroblastic reticular cells and T cells in the adult mouse spleen. [Proc Natl Acad Sci USA] Abstract

Circadian Clock Cryptochrome Proteins Regulate Autoimmunity

Scientists showed that mice deficient of the circadian clock genes Cry1 and Cry2 develop an autoimmune phenotype including high serum IgG concentrations, serum antinuclear antibodies, and precipitation of IgG, IgM, and complement 3 in glomeruli and massive infiltration of leukocytes into the lungs and kidneys. [Proc Natl Acad Sci USA] Abstract

Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance

Investigators found that IL-35-producing Tregs were a distinct effector population from the IL-10-producing subset. They also revealed that these two subsets of effector Tregs have different transcription factor dependency. [Cell Rep] Full Article | Graphical Abstract

Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells

Researchers showed that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3⁺ Treg cells with defective in vivo proliferative capacity. [Cell Rep] Full Article | Graphical Abstract

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The Diverse Functions of the PD1 Inhibitory Pathway

The authors discuss the diverse roles of the programmed cell death protein 1 (PD1) pathway in regulating immune responses and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation. [Nat Rev Immunol] Full Article

Achievements and Obstacles of Remyelinating Therapies in Multiple Sclerosis

Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for multiple sclerosis are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials. [Nat Rev Neurol] Abstract

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Cue Biopharma Announces Strategic Research Collaboration and License Agreement with Merck

Cue Biopharma^™, Inc. announced a strategic research collaboration and license agreement with Merck, known as MSD outside of the United States and Canada. [Cue Biopharma^™, Inc.] Press Release

Evelo Biosciences and Mayo Clinic Collaborate to Advance Monoclonal Microbials for the Treatment of Inflammatory and Neuroinflammatory Diseases

Evelo Biosciences announced a collaboration with Mayo Clinic to develop and commercialize monoclonal microbials for the treatment of inflammatory and neuroinflammatory diseases. [Evelo Biosciences, Inc. (PR Newswire Association LLC.)] Press Release

FDA Announces Comprehensive Regenerative Medicine Policy Framework

The FDA announced a comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies. The framework – outlined in a suite of four guidance documents – builds upon the FDA’s existing risk-based regulatory approach to more clearly describe what products are regulated as drugs, devices, and/or biological products. [U.S. Food and Drug Administration] Press Release

African Scientists Get Their Own Open-Access Publishing Platform

Africa’s academy of science has announced that it will launch an open-access publishing platform — the first of its kind aimed exclusively at scientists on the continent. [Nature News] Editorial

Graduate Students Face Alarming Tax Hike

The last thing that graduate students need is a tax hike. But that is what many would face under a clause in the federal-tax-reform bill passed by the US House of Representatives. It will need to be reconciled with the Senate’s tax-reform bill (which retains many existing student tax benefits), and signed by the president. [Nature News] Editorial

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