Immune Regulation News Volume 10.16 | May 4 2018

TOP STORY

Atherogenic Dyslipidemia Promotes Autoimmune Follicular Helper T Cell Responses via IL-27

Scientists found that reconstitution of atherosclerosis-prone Apoe^–/– and Ldlr^–/– mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. [Nat Immunol] Abstract

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Role of Human FOXP3 in Early Thymic Maturation and Peripheral T Cell Homeostasis

The authors evaluated the effect of reduced FOXP3 expression on human Treg and effector T cell development and correlate it with the IPEX immune pathology. [J Allergy Clin Immunol] Abstract

Nox2 in Regulatory T Cells Promotes Angiotensin II-Induced Cardiovascular Remodeling

Researchers investigated the role of Nox2 in T cells, particularly Tregs. Mice globally deficient in Nox2 displayed increased numbers of Tregs in the heart at baseline whereas angiotensin II-induced T-effector cell infiltration was inhibited. [J Clin Invest] Abstract | Full Article

IL-21 Drives Expansion and Plasma Cell Differentiation of Autoreactive CD11c^hiT-bet⁺ B Cells in SLE

Investigators showed that an unusual CD11c^hiT-bet⁺ B cell subset, with a unique expression profile including chemokine receptors consistent with migration to target tissues, was expanded in systemic lupus erythematosus (SLE) patients, present in nephrotic kidney, enriched for autoreactive specificities and correlates with defined clinical manifestations. [Nat Commun] Full Article

Revealing the Specificity of Regulatory T Cells in Murine Autoimmune Diabetes

Investigators showed an accumulation of antigen-experienced Tregs in the inflamed islets using a mouse model of autoimmune diabetes. MHC tetramer staining and single-cell T cell receptor analyses of islet Tregs revealed their specificity for insulin and other islet-derived antigens. [Proc Natl Acad Sci USA] Abstract

TK Inhibitor Pazopanib Primes DCs by Downregulation of the β-Catenin Pathway

The authors investigated the influence of the Tyrosine kinase inhibitor pazopanib on dendritic cell (DC) performance and immune priming. Pazopanib improved DC differentiation and performance by promoting upregulation of the maturation markers HLA-DR, CD40, and CCR7; decreasing IL10 production and endocytosis; and increasing T-cell proliferation. [Cancer Immunol Res] Abstract | Full Article

The Interaction between IKKα and LC3 Promotes Type I Interferon Production through the TLR9-Containing LAPosome

Researchers showed that after the stimulation of Toll-like receptor 9 (TLR9) by CpG oligonucleotides, the autophagy protein light chain 3 (LC3) and the kinase IKKα were recruited to endosomes that contained TLR9. The recruitment of IKKα and LC3 to such signaling endosomes was not stimulated by catalysts of classical autophagosome formation but involved LC3-associated phagocytosis (LAP) formation, which required ATG5 but not FIP200. [Sci Signal] Abstract

Pathological Conversion of Regulatory T Cells Is Associated with Loss of Allotolerance

Using a double transgenic mouse model that permits Foxp3 lineage tracing, scientists investigated the phenotypic plasticity of Foxp3⁺ Tregs in a well-characterized murine model of corneal transplantation. [Sci Rep] Full Article

Egr2-Independent, Klf1-Mediated Induction of PD-L1 in CD4⁺ T Cells

The authors revealed the potential function of Klf1 and Egr2-mediated induction of programmed death ligand 1 (PD-L1) in CD4⁺ T cells. They focused on the molecules specifically expressed in CD4⁺CD25⁻LAG3⁺ regulatory T cells highly express of PD-L1 and transcription factor Egr2. [Sci Rep] Full Article

Blimp-1 Prolongs Allograft Survival without Regimen via Influencing T Cell Development in Favor of Regulatory T Cells while Suppressing Th1

Without any immunosuppression, fully MHC-mismatched skin allografts on Tg⁺ mice had a significantly prolonged survival rate and partial tolerance at 90 days. Allograft lymphocytic infiltration was decreased in Tg⁺ mice and a dampened donor-stimulated alloimmune response was seen. [Mol Immunol] Abstract

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The Pathogenicity of IL-33 on Steroid-Resistant Eosinophilic Inflammation via the Activation of Memory-Type ST2⁺CD4⁺ T Cells

The authors discuss the impact of ST2J+CD4⁺ T cells on shaping the pathology of IL-33-induced eosinophilic inflammation. They also highlight the mechanism underlying steroid resistance in eosinophilic pneumonia. [J Leukoc Biol] Abstract

The Opposing Roles of CD4⁺ T Cells in Anti-Tumor Immunity

Investigators highlight opposing mechanisms of conventional and Treg at both sites. They outline how current cancer immunotherapy strategies affect both subsets and how selective modulation of each subset is important to maximize the clinical response of cancer patients. [Immunology] Abstract | Full Article

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

Kymriah^® (Tisagenlecleucel), First-in-Class CAR-T Therapy from Novartis, Receives Second FDA Approval to Treat Appropriate r/r Patients with Large B-Cell Lymphoma

Novartis announced the FDA has approved Kymriah^® suspension for intravenous infusion for its second indication – the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. [Novartis Pharmaceuticals Corporation] Press Release

Genocea Files Investigational New Drug Application for Neoantigen Cancer Vaccine Candidate GEN-009

Genocea Biosciences, Inc. announced the filing of an Investigational New Drug Application with the FDA to begin a Phase I/IIa clinical program testing the safety, immunogenicity, and clinical efficacy of GEN-009, the company’s lead personalized neoantigen cancer vaccine candidate. [Genocea Biosciences, Inc.] Press Release

Cellectis Files IND for UCART22 in Acute Lymphoblastic Leukemia (B-ALL)

Cellectis announced that the company has submitted an Investigational New Drug (IND) application to the FDA requesting approval to initiate a Phase I clinical trial for UCART22, Cellectis’ second wholly controlled TALEN^® gene-edited product candidate, for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) in adult patients. [Cellectis] Press Release

Nature Announces New Editor-in-Chief

Nature has named Magdalena Skipper as its new editor-in-chief. She is the first woman to hold the post. Skipper, who is currently editor-in-chief of the open-access journal Nature Communications, will become the eighth editor of Nature. [Nature News] Editorial

Big UK Science Funder Says Report Harassment or Risk Losing Funding

One of the world’s largest research-funding charities is cracking down on harassment and bullying. Scientists who have been sanctioned by their institutions could lose out on funding from the Wellcome Trust, under rules announced. [Nature News] Editorial

Nature Journals Formalize Ethical Standards for Human Embryo and Stem-Cell Research

Nature journals encourage stem-cell scientists to embrace guidelines agreed in 2016 by the International Society for Stem Cell Research as they design, execute and report their research. [Nature News] Editorial

Accused Cancer Scientist Resigns as Editor of Prestigious Journal

Inder Verma, the prominent cancer scientist and geneticist who has been accused of sexual harassment by several women, resigned yesterday as editor-in-chief of the Proceedings of the National Academy of Sciences, a prestigious academic journal. [ScienceInsider] Editorial

NEW 2^nd AACR International Conference: Translational Cancer Medicine
September 27-29, 2018
Sao Paulo, Brazil

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

NEW Computational Scientist – Immune System (Karolinska Institutet)

NEW Immunologist – Project Research (The Francis Crick Institute)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow/Research Associate – Immune Modulatory Therapies (Houston Methodist Hospital)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Research Scientist – Biomarker Development (Kymab)

Postdoctoral Fellow – Immune Suppression Mechanisms in Myeloid Cells (AstraZeneca)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Scientist – Immune Tolerance (Moderna Therapeutics)

Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

Postdoctoral Associate Position – Tumor Immunology/Immunotherapy (Duke Cancer Institute)

Assistant, Associate, or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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