Immune Regulation News Volume 9.08 | Mar 3 2017

TOP STORY

Essential Role for the Transcription Factor Bhlhe41 in Regulating the Development, Self-Renewal and BCR Repertoire of B-1a Cells

The authors identified an essential role for the transcription factor Bhlhe41, with a lesser contribution by Bhlhe40, in controlling B-1a cell differentiation. [Nat Immunol] Abstract

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Potassium Channels Kv1.3 and KCa3.1 Cooperatively and Compensatorily Regulate Antigen-Specific Memory T Cell Functions

Scientists showed, using Kv1.3-deficient rats, that Kv1.3 is involved in the development of chronically activated antigen-specific T cells. Several immune responses are normal in Kv1.3 knockout rats, suggesting that KCa3.1 can compensate for the absence of Kv1.3 under these specific settings. [Nat Commun] Full Article

Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma

The authors evaluated percentages of CD38-expressing subsets in Tregs from normal donors and multiple myeloma patients. PBMCs were then treated with isatuximab with or without lenalidomide or pomalidomide to identify their impact on percentage and immunosuppressive activity of Tregs on CD4⁺CD25^– T cells. [Clin Cancer Res] Abstract

Origin of Enriched Regulatory T Cells in Patients Receiving Combined Kidney/Bone Marrow Transplantation to Induce Transplantation Tolerance

Polychromatic flow cytometry and high throughput sequencing of TCRβ hypervariable regions of DNA from peripheral blood T regulatory cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of regulatory T cells in blood that resulted from peripheral proliferation, possibly new thymic emigration and, in one tolerant subject, conversion from non-Tregs. [Am J Transplant] Abstract

Mesenchymal Stromal Cells Inhibit CD25 Expression via the mTOR Pathway to Potentiate T-Cell Suppression

Researchers showed that mesenchymal stromal cells (MSCs) inhibited CD25 expression, which was restored in the presence of an inducible nitric oxide synthase inhibitor. Since CD25 mRNA expression was not inhibited, they focused on determining whether MSCs modulated components of the mTOR pathway in T cells. [Cell Death Dis] Full Article

Metformin Suppresses Systemic Autoimmunity in Roquin^san/san Mice through Inhibiting B Cell Differentiation into Plasma Cells via Regulation of AMPK/mTOR/STAT3

Scientists assessed the effect of metformin, which inhibits mechanistic target of rapamycin (mTOR), on the development of autoimmunity using Roquin^san/san mice. Oral administration of metformin inhibited the formation of splenic follicles and inflammation in kidney and liver tissues. [J Immunol] Abstract | Full Article

IL-6 Production by TLR-Activated APC Broadly Enhances Aged Cognate CD4 Helper and B Cell Antibody Responses In Vivo

Researchers found that using APC pretreated ex vivo with TLR agonists, polyinosinic-polycytidylic acid and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG Ab production. [J Immunol] Abstract

Novel CD28 Antagonist mPEG PV1-Fab’ Mitigates Experimental Autoimmune Uveitis by Suppressing CD4⁺ T Lymphocyte Activation and IFN-γ Production

Investigators showed that PV1-Fab’ treatment decreases both average disease score and incidence of experimental autoimmune uveitis. A decrease in the activation profile of both T CD4⁺ and T CD8⁺ eye-infiltrating lymphocytes was evidenced. [PLoS One] Full Article

Macrophage Regulation of B Cell Proliferation

The authors assessed the ability of peritoneal cavity (PerC) B cells to respond to surrogate activating signals in the presence of high numbers of macrophages. Surface IgM (BCR) ligation led to cyclooxygenase-mediated, and TLR-4 ligation to IL10-mediated, suppression of PerC B cell proliferation. [Cell Immunol] Abstract

Reduced Inflammatory Responses of Follicular Helper T Cell Promote the Development of Regulatory B Cells after Roux-en-Y Gastric Bypass

Scientists found that the follicular helper T (Tfh) cells after Roux-en-Y gastric bypass (RYGB) were not significantly changed in number, but presented altered cytokine secretion profile, including lower interferon-γ, interleukin (IL)-2, IL-4, and IL-17 secretion. Tfh cells after RYGB also downregulated inducible co-stimulator and programmed death-1. [Clin Exp Pharmacol Physiol] Abstract

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Amino-Acid Transporters in T-Cell Activation and Differentiation

The authors present current information on amino-acid transporters, such as L-leucine transporter, L-glutamine transporter and γ-aminobutyric acid transporter-1, which are critically important for mediating peripheral naive T-cell homeostasis, activation and differentiation, especially for Th1 and Th17 cells, and even memory T cells. [Cell Death Dis] Full Article

Heterogeneity of Toll-Like Receptor 9 Signaling in B Cell Malignancies and Its Potential Therapeutic Application

The authors summarize current understanding of the heterogeneity in responses of normal and malignant B cells to Toll-like receptor 9 (TLR9) agonists, due to differences in TLR9 expression levels, genetic alterations, and signaling pathway activation. [J Transl Med] Full Article

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University of Pennsylvania Announces Cancer Research Alliance with Incyte

The University of Pennsylvania and Incyte Corporation have announced a research alliance to propel advances in cancer biology and immunotherapy. [The University of Pennsylvania] Press Release

EnGeneIC Receives FDA Orphan Drug Designation for Targeted EDV™ Nanocells to Treat Glioblastoma Multiforme

EnGeneIC Ltd. announced that U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to EGFR-targeted, doxorubicin-loaded EDV nanocells for the treatment of glioblastoma multiforme. [EnGeneIC Ltd.] Press Release

Regen BioPharma, Inc. Licenses NR2F6 Technology for Cancer Treatment and Autoimmune Disorders to CheckPoint Immunology Inc.

Regen BioPharma Inc. has granted CheckPoint Immunology Inc. an exclusive worldwide license to develop and commercialize Regen’s NR2F6 technology for human therapeutic use. [Regen BioPharma Inc. (PR Newswire Association LLC.)] Press Release

How the Fallout from Trump’s Travel Ban Is Reshaping Science

Many foreign-born scientists say they are reconsidering plans to work or study in the United States, even though federal courts have indefinitely blocked US President Donald Trump’s travel ban. The policy, which Trump signed on 27 January, sought to deny entry to citizens of seven Muslim-majority nations for 90 days — including those with valid US visas. [Nature News] Editorial

Peer-Review Activists Push Psychology Journals towards Open Data

An editor on the board of a journal published by the prestigious American Psychological Association has been asked to resign in a controversy over data sharing in peer review. Gert Storms — who says he won’t step down — is one of a few hundred scientists who have vowed that, from the start of this year, they will begin rejecting papers if authors won’t publicly share the underlying data, or explain why they can’t. [Nature News] Editorial

Senior Republican Lawmaker Has Some Advice for U.S. Science Marchers

The chairman of a congressional spending panel that oversees a wide swath of U.S. science agencies has some unusual advice for scientists planning to march on 22 April: Don’t talk about research. Instead, demand that Congress find a way to cut mandatory spending programs. [ScienceInsider] Editorial

NEW Immunology 2017
May 12-16, 2017
Washington, United States

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NEW Postdoctoral Position(s) – HIV-1 Research (Aarhus University)

NEW Principal Scientist – Immuno Oncology (Celgene Corporation)

Research Technologist – Cell Separation & Immunology (STEMCELL Technologies, Inc.)

Postdoctoral Researcher – Development of Immune System (Lund University)

Research Investigator – Immuno-Oncology (Bristol-Meyers Squibb)

Associate/Full Professor – Immunobioengineering (University of Toronto)

Scientist – Immunology (Moderna Therapeutics)

Postdoctoral Fellow – Immunology (Institute of Molecular and Cell Biology)

Senior Scientist – (Immatics Biotechnologies GmbH)

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

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

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