Immune Regulation News Volume 8.21 | Jun 10 2016

TOP STORY

Tissue Adaptation of Regulatory and Intraepithelial CD4⁺ T Cells Controls Gut Inflammation

Using intravital microscopy, researchers showed distinct cell dynamics of intestinal regulatory T cell (T_regs) and CD4_IELs. Upon migration to the epithelium, T_regs lose Foxp3 and convert to intraepithelial CD4⁺ T cells (CD4_IELs) in a microbiota-dependent fashion, an effect attributed to the loss of the transcription factor ThPOK. [Science] Abstract

(Ranked by impact factor of the journal)

Control of the Innate Immune Response by the Mevalonate Pathway

Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. Investigators found that protein geranylgeranylation enabled Toll-like receptor-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. [Nat Immunol] Abstract

RNAi Targeting Multiple Cell Adhesion Molecules Reduces Immune Cell Recruitment and Vascular Inflammation after Myocardial Infarction

Scientists showed that, in ApoE^−/− mice with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression of adhesion molecules. [Sci Transl Med] Abstract

Anti-TNF Drives Regulatory T Cell Expansion by Paradoxically Promoting Membrane TNF-TNF-RII Bindin-G in Rheumatoid Arthritis

Investigators showed that the therapeutic anti-tumor necrosis factor (TNF) antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis. [J Exp Med] Abstract

Constitutive Lck Activity Drives Sensitivity Differences between CD8⁺ Memory T Cell Subsets

Researchers showed in mouse effector memory T cells that greater than 50 percent of lymphocyte-specific protein tyrosine kinase (Lck) exists in a constitutively active conformation, compared with less than 20 percent in central memory T cells. [J Exp Med] Abstract

Deep-Phenotyping of Tregs Identifies an Immune Signature for Idiopathic Aplastic Anemia and Predicts Response to Treatment

Researchers aimed to characterize regulatory T cell (Treg) subpopulations in aplastic anemia and investigate the potential correlation between specific Treg subsets and response to immunosuppressive therapy as well as their in-vitro expandability for potential clinical use. [Blood] Abstract

T Cell Activation Requires Force Generation

Triggering of the T cell receptor integrates both binding kinetics and mechanical forces. To understand the contribution of the T cell cytoskeleton to these forces, scientists triggered T cells using a novel application of atomic force microscopy. [J Cell Biol] Abstract

The PD-1/PD-L1 Inhibitory Pathway Is Altered in Pre-Eclampsia and Regulates T Cell Responses in Pre-Eclamptic Rats

Researchers observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of programmed cell death-1(PD-1) and PD-ligand 1 (PD-L1) on the two subsets also changed in pre-eclampsia compared with normal pregnancy. [Sci Rep] Full Article

Significant Decrease in Peripheral Regulatory B Cells Is an Immunopathogenic Feature of Dermatomyositis

The authors performed flow cytometry analysis of studied CD19⁺ CD24^highCD38^high Breg subpopulations in blood samples from 30 patients with dermatomyositis, 37 diseased controls and 23 healthy controls. [Sci Rep] Full Article

MiRNAs Regulate T Cell Production of IL-9 and Identify Hypoxia Inducible Factor-2α (HIF-2α) as an Important Regulator of Th9 and Treg Differentiation

Two highly related miRNAs (miR-15b and miR-16) that the authors previously found to play an important role in regulatory T cell (Treg) differentiation were capable of suppressing IL-9 expression when they were overexpressed in Th9 cells. They used these miRNAs as tools to identify novel regulators of IL-9 expression and found they could regulate the expression of Epas1, which encodes hypoxia inducible factor (HIF)-2α. [Immunology] Abstract

Macrophages Transfer Antigens to DCs by Releasing Exosomes Containing Dead Cell-Associated Antigens Partially through Ceramide-Dependent Pathway to Enhance CD4⁺ T Cell Response

By transferring high numbers of dead cells to mimic a failure of apoptotic cell clearance in vivo, scientists found that Mφs and neutrophils were predominant phagocytes in the uptake of dead cells in the spleen. Moreover, both Mφs and dendritic cells (DCs) were required for an optimal CD4⁺ T cell response triggered by dead cell-associated antigens. [Immunology] Abstract

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CD8⁺ T Cells in Human Autoimmune Arthritis: The Unusual Suspects

The reviewers assess the link between CD8⁺ T cells, autoimmune arthritis and the basis of their homeostatic changes under inflammatory conditions. Improved insight into CD8⁺ T cell-specific pathogenicity will be essential for a better understanding of autoimmune arthritis and the identification of new therapeutic targets. [Nat Rev Rheumatol] Abstract

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

Preclinical Data Presented Demonstrate that Single-Agent NKTR-214 Produces a Large Increase in Tumor-Infiltrating Lymphocytes to Provide Durable Anti-Tumor Activity

Nektar Therapeutics announced new preclinical data for NKTR-214, an immuno-stimulatory CD-122 biased cytokine currently being evaluated in cancer patients with solid tumors in a Phase I/II clinical trial being conducted at MD Anderson Cancer Center and Yale Cancer Center. The new preclinical data presented demonstrate that treatment with single-agent NKTR-214 mobilizes tumor-killing T cells into colon cancer tumors. [Press release from Nektar Therapeutics discussing research presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Study Shows Why Immune-Boosting Therapy Doesn’t Work for Everyone with Widespread Melanoma

A study found that a pattern of “gene dysregulation” causes immune T cells to turn back to an immature state, making the cells less effective against metastatic melanoma, a deadly form of skin cancer. Such “immunotherapies” work by enhancing, not disrupting, the ability of T cells to identify and destroy cancer cells the way they would an invading virus. [Press release from NYU Langone Medical Center (EurekAlert!) discussing research presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

Daratumumab Significantly Extended Progression-Free Survival in Combination with Lenalidomide and Dexamethasone in Patients with Multiple Myeloma

Janssen Research & Development, LLC announced data from the Phase III MMY3003 (POLLUX) trial, which show the immunotherapy daratumumab in combination with a standard-of-care treatment regimen, lenalidomide and dexamethasone, achieved a 63 percent reduction in the risk of disease progression or death compared to lenalidomide and dexamethasone alone in patients with multiple myeloma who had received at least one prior line of therapy. [Janssen Research & Development, LLC] Press Release

Exceptional Early-Career Scientists Named Pew Scholars in the Biomedical Sciences

The Pew Charitable Trusts named 22 exceptional early-career scientists as Pew scholars in the biomedical sciences. The 2016 class of Pew biomedical scholars is drawn from prestigious institutions across the country, with each scholar receiving four years of flexible funding to pursue foundational, innovative research. [The Pew Charitable Trusts] Press Release

NEW International Conference on Stem Cell Engineering 2016
October 23-26, 2016
Toronto, Canada

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

NEW Postdoctoral Scientist – Novel Immune Modulating Drugs (Celenlyx)

NEW Research Associate – TNF Blockade Regulates of IL-10 (King’s College London)

Technical Sales Representative (STEMCELL Technologies Inc.)

Research Technologist – T Cell Immunology (STEMCELL Technologies Inc.)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Bioengineering (STEMCELL Technologies Inc.)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

PhD Position or Postdoctoral Fellowship – Immunology with Focus on Autoimmunity (University of Oslo)

Postdoctoral/Senior Postdoctoral Fellow Positions – CD8 Biology, CD4 Plasticity, and T Cell Receptor Signaling (Georgia Cancer Center)

Postdoctoral Position – Transforming Growth Factor β on the Regulation of T Cell Response (Inserm)

Post Doctoral Research – Fellow Thymic and Immune Regeneration (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Immunology (New York University Medical Center)

Postdoctoral Position – Regulation of γδ T Cell Phenotype and Trafficking in Breast Cancer Metastasis (Cancer Research UK Beatson Institute)

Faculty Positions – Microbiology and Immunology (National University of Singapore)

Postdoctoral Researchers – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

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