Immune Regulation News Volume 8.36 | Sep 30 2016

TOP STORY

TRIM14 Inhibits cGAS Degradation Mediated by Selective Autophagy Receptor p62 to Promote Innate Immune Responses

Investigators report that K48-linked ubiquitination of cyclic GMP-AMP synthase (cGAS) is a recognition signal for p62-dependent selective autophagic degradation. The induction of TRIM14 by type I interferon accelerates cGAS stabilization by recruiting USP14 to cleave the ubiquitin chains of cGAS at lysine (K) 414. [Mol Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

FOXP3⁺ Tregs Require WASP to Restrain Th2-Mediated Food Allergy

Researchers showed that Wiskott-Aldrich syndrome (WAS) patients and mice deficient in WAS protein (WASP) frequently develop IgE-mediated reactions to common food allergens. WASP-deficient animals displayed an adjuvant-free IgE-sensitization to chow antigens that was most pronounced for wheat and soy and occurred under specific pathogen–free as well as germ-free housing conditions. [J Clin Invest] Full Article

Efficient Plasma Cell Differentiation and Trafficking Require Cxcr4 Desensitization

Using a knockin mouse model phenocopying WHIM syndrome, the authors showed that, counter-intuitively, a gain of Cxcr4 function inhibited the maintenance of antibody titers after immunization. [Cell Rep] Full Article | Graphical Abstract

PTPN2-Deficiency Exacerbates T Follicular Helper Cell and B Cell Responses and Promotes the Development of Autoimmunity

The authors showed that the inducible deletion of PTPN2 in hematopoietic compartment of adult non-autoimmune prone mice results in systemic inflammation and autoimmunity. PTPN2-deficient mice had increased inflammatory monocytes, B cells and effector T cells in lymphoid and non-lymphoid tissues and exhibited symptoms of dermatitis, glomerulonephritis, pancreatitis and overt liver disease. [J Autoimmun] Abstract

A Role for Peroxisome Proliferator-Activated Receptor Beta in T Cell Development

Using both in vivo and in vitro models, researchers demonstrated that PPARβ activation/overexpression inhibits thymic T cell development by decreasing proliferation of CD4⁻CD8⁻ double-negative stage 4 thymocytes. [Sci Rep] Full Article

Antigen-Specific Development of Mucosal Foxp3⁺RORγt⁺ T Cells from Regulatory T Cell Precursors

Investigators used a fixed TCRβ system to show that the TCR repertoire of the Foxp3⁺ retinoic acid–related orphan receptor (ROR)γt⁺ population is mostly distinct compared with other colonic T cell subsets. However, of these TCRs, a fraction is also found in the Th17 subset, suggesting that TCR repertoire overlap may contribute to the reported ability of Foxp3⁺RORγt⁺ cells to regulate Th17 immunity. [J Immunol] Abstract

Antigen-Specific Immune Modulation Targets mTORC1 Function to Drive Chemokine Receptor–Mediated T Cell Tolerance

Investigators showed that the mammalian target of rapamycin complex 1 (mTORC1) is a major target for induction of CXCR3 downregulation and crippling of Th1 cells. Ag administration induces upregulation of programmed death-ligand 1 on dendritic cells in a T cell–dependent manner. [J Immunol] Abstract

Anti-PD-1 Inhibits Foxp3⁺ Treg Cell Conversion and Unleashes Intratumoral Effector T Cells thereby Enhancing the Efficacy of a Cancer Vaccine in a Mouse Model

The authors examined the role of PD-1 in regulating the balance between regulatory and effector T cells and whether blocking PD-1 could enhance tumor vaccine-induced protective immunity. [Cancer Immunol Immunother] Abstract

Foxp3 Promotor Methylation Impairs Suppressive Function of Regulatory T Cells in Biliary Atresia

Focusing on why the suppressive function of Treg was impaired, scientists found out methylation status of CpG islands within the Foxp3 promotor of Tregs in biliary atresia patients and murine models were both increased. [Am J Physiol Gastrointest Liver Physiol] Abstract

Adoptive Regulatory T-Cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage

Scientists investigated the effect of regulatory T cells (Tregs) on brain injury using the mouse intracerebral hemorrhage (ICH) model, which is established by autologous blood infusion. They showed that tail intravenous injection of Tregs significantly reduced brain water content and Evans blue dye extravasation of perihematoma at day 1,3 and 7, and improved short- and long-term neurological deficits following ICH in mouse model. [Cell Mol Neurobiol] Abstract

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Emerging Roles of p53 and Other Tumor-Suppressor Genes in Immune Regulation

The authors discuss the emerging roles of p53 and other tumour-suppressor genes in tumor immunology, as well as in additional immunological settings, such as virus infection. [Nat Rev Immunol] Abstract

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Two New Trials of Merck’s KEYTRUDA^® (Pembrolizumab) as Monotherapy and in Combination with Chemotherapy for First-Line Treatment of Patients with Advanced Non-Small Cell Lung Cancer to Be Presented

Merck announced that extensive data on KEYTRUDA^®, the company’s anti-PD-1 therapy, have been accepted for presentation. [Press release from Merck & Co., Inc. discussing research to be presented at the European Society for Medical Oncology (ESMO) 2016 Congress, Copenhagen] Press Release

Zymeworks and Daiichi Sankyo Announce Immuno-Oncology Cross-Licensing Agreement and Bi-Specific Antibody Collaboration

Zymeworks Inc. and Daiichi Sankyo Company, Limited announced that they have entered into a cross-licensing and collaboration agreement to develop proprietary cancer immuno-oncology products. [Zymeworks Inc.] Press Release

BeyondSpring Announces First Patient Enrolled in Phase Ib/II Investigator-Initiated Trial of Plinabulin plus Nivolumab for Non-Small Cell Lung Cancer

BeyondSpring Pharmaceuticals announced that the first patient in the Phase Ib/II trial of its lead immuno-oncology asset Plinabulin in combination with Nivolumab, an immune-checkpoint inhibitor, in patients with metastatic non-small cell lung cancer was enrolled. [BeyondSpring Pharmaceuticals, Inc.] Press Release

Biologists Plan Scoring System for Antibodies

Biomedical experts plan to create a scoring system that will help researchers choose reliable antibodies for their experiments. The only problems: figuring out how such a ranking would work — and getting manufacturers to adopt the standard. [Nature News] Editorial

UK Bioethicists Eye Designer Babies and CRISPR Cows

From designer babies to engineered mosquitoes, advances in genome-editing technologies such as CRISPR–Cas9 have raised the possibility of tremendous scientific advances — and serious ethical concerns. [Nature News] Editorial

Science Spending Boosted in French Budget

France’s government has proposed an unusually generous boost to research and higher education in its 2017 draft budget. This is the largest increase for 15 years,” Thierry Mandon, France’s research and higher-education minister, told reporters at a press conference. [Nature News] Editorial

Open-Access Journal eLife to Start Charging Fees

The open-access journal eLife is dropping one of its most distinctive features: free publishing. From 2017, it will charge a fee of $2,500 for all accepted papers. [Nature News] Editorial

Can Cuban Science Go Global?

Tensions between Cuba and the United States are easing. But researchers still struggle to join the scientific world. [Nature News] Editorial

Validate Your Antibodies to Improve Reproducibility? Easier Said than Done

More than 100 researchers, antibody manufacturers, journal editors, and funders met in Pacific Grove, California, to hash out standardized approaches to antibody testing. [Science Insider] Editorial

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