Immune Regulation News Volume 8.35 | Sep 23 2016

TOP STORY

Pioneering Research Points to a New Class of Targets for Cancer and Immune Diseases

It’s well known that the epithelial cells that line the surface of our skin and our gut provide physical and chemical barriers against dirt and pathogens. What’s less well known is that they also provide a home to complex immune cell compartments that carry out tissue-based immune surveillance – like a guard providing security at a particular location versus a policeman on patrol. [Press release from The Francis Crick Institute discussing online prepublication in Cell] Press Release | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation

Investigators report that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for follicular helper T cell differentiation and germinal center reaction under steady state and after antigen immunization and viral infection. [Immunity] Abstract | Graphical Abstract

Aging Promotes Acquisition of Naive-Like CD8⁺ Memory T Cell Traits and Enhanced Functionalities

Comprehensive molecular, phenotypic, and functional profiling of aging antiviral CD8⁺ memory T cells (CD8⁺ T_M) revealed a pervasive remodeling process that promotes the gradual acquisition of distinct molecular signatures, of increasingly homogeneous phenotypes, and of diversified functionalities that combine to confer a CD8⁺ T_M–autonomous capacity for enhanced recall responses and immune protection. [J Clin Invest] Full Article

Suppression of T Cell Autophagy Results in Decreased Viability and Function of T Cells through Accelerated Apoptosis in a Murine Sepsis Model

The authors investigated the kinetics of autophagy in T cells from spleen in a cecal ligation and puncture model with green fluorescent protein-microtubule-associated protein light chain 3 transgenic mice. They analyzed apoptosis, mitochondrial homeostasis and cytokine production in T cells, and survival rate after cecal ligation and puncture using T cell-specific autophagy-deficient mice. [Crit Care Med] Abstract

Complement Component 3 Deficiency Prolongs MHC-II Disparate Skin Allograft Survival by Increasing the CD4⁺ CD25⁺ Regulatory T Cells Population

Researchers investigated the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3^−/−) as skin graft donors or recipients. Compared with C3^+/+ B6 allografts, C3^−/− B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2^bm12 B6 recipients, indicating that C3 plays a critical role in allograft rejection. [Sci Rep] Full Article

Transmission of Survival Signals through Delta-Like 1 on Activated CD4⁺ T Cells

The authors demonstrated that the CD4⁺ T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4⁺ T cells from Dll1^−/− and control mice into recipient mice followed by immunization revealed a rapid decline of CD4⁺ T cells from Dll1^−/− mice compared with control cells. [Sci Rep] Full Article

Inhibition of Acid Sphingomyelinase Allows for Selective Targeting of CD4⁺ Conventional versus Foxp3⁺ Regulatory T Cells

Scientists showed that the basal and CD28-induced Asm activity is higher in regulatory T cells (Tregs) than in conventional CD4⁺ T cells of wild-type (wt) mice. In Asm-deficient mice, as compared with wt mice, the frequency of Tregs among CD4⁺ T cells, turnover of the effector molecule CTLA-4, and their suppressive activity in vitro were increased. [J Immunol] Abstract

High-Dose Wogonin Exacerbates DSS-Induced Colitis by Up-Regulating Effector T Cell Function and Inhibiting Treg Cell

Scientists identified that high-dose wogonin could inhibit the growth of transplanted tumors by directly inducing tumor apoptosis and promoting DC, T and NK cell recruitment into tumor tissues to enhance immune surveillance. [J Cell Mol Med] Full Article

CD4⁺Foxp3⁻ Type 1 Regulatory T Cells in Glioblastoma Multiforme Suppress T Cell Responses through Multiple Pathways and Are Regulated by Tumor Associated Macrophages

The authors examined the frequency, phenotype, induction mechanism, and function of type 1 regulatory T (Tr1) cells in glioblastoma multiforme (GBM) patients. Compared to healthy controls, GBM patients presented significantly higher frequency of Tr1 cells in peripheral blood. [Int J Biochem Cell Biol] Abstract

HLA-G and CD8⁺ Regulatory T Cells in the Inflammatory Environment of Preeclampsia

Investigators addressed the role of HLAG gene polymorphisms and protein expression as well as regulatory T cells and Th1/Th2/Th17 cytokines in healthy and pathological pregnancies. [Reproduction] Abstract

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TNFα in the Regulation of Treg and Th17 Cells in Rheumatoid Arthritis and other Autoimmune Inflammatory Diseases

The authors summarize knowledge on how TNFα modulates T cell responses and the effect of engaging either of its two receptors. Furthermore, they discuss how such interactions can dictate the outcome of treatment with TNFα inhibitors. [Cytokine] Abstract

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

Cidara Therapeutics Selects First Development Candidate from its Cloudbreak™ Immunotherapy Discovery Platform

Cidara Therapeutics, Inc. announced that the company has selected the first development candidate from its proprietary immunotherapy discovery platform, Cloudbreak™. Cloudbreak is the first platform of its kind designed specifically to create compounds that direct a patient’s immune cells to attack and eliminate bacterial, fungal or viral microbial pathogens. [Cidara Therapeutics, Inc.] Press Release

Kadmon Initiates Placebo-Controlled Phase II Clinical Trial Evaluating KD025 in Psoriasis

Kadmon Holdings, Inc. announced that the first patient has been dosed in a double-blind, placebo-controlled Phase II clinical trial of KD025, the company’s oral inhibitor of Rho-associated coiled-coil kinase 2, in moderate to severe chronic plaque psoriasis. [Kadmon Holdings, Inc.] Press Release

ASIT Biotech Announces the Initiation of a Phase IIa Clinical Study of Its Second Product Candidate hdm-ASIT+™ for House Dust Mite Rhinitis

ASIT biotech announced that its Phase IIa trial with hdm-ASIT+™ for house dust mite rhinitis has been approved by the German Competent Authority and the Ethic Committee of the Technical University Dresden. [ASIT Biotech] Press Release

BioInvent Expands Patent Approvals for its Lead Clinical Immuno-Oncology Program in Multiple Myeloma, BI-505

BioInvent International announced that it has been granted additional patent protection in Japan, Russia and China for BI-505, its lead immune-oncology program currently in Phase II for the treatment of multiple myeloma. [BioInvent International] Press Release

Titanic Clash over CRISPR Patents Turns Ugly

Much of the focus is on the teams centred at Berkeley and the Broad Institute, whose ‘foundational’ patents cover a wide swathe of CRISPR–Cas9 applications. Although Berkeley’s team filed for a patent first, the Broad opted for an expedited review process, and its patents were granted earlier. [Nature News] Editorial

Spain Joins Bandwagon for ‘Openness’ About Animal Research

The Spanish scientific community has pledged to become more transparent about animal research. Ninety research centers, universities, scientific societies, and companies around Spain have adopted a set of standards, launched by the Confederation of Spanish Scientific Societies, on how research organizations should open up communication channels about their use of laboratory animals. [Science Insider] Editorial

New Fellowship Aims to Increase Diversity in the Life Sciences

A new program aims to launch the careers of life scientists from underrepresented groups by providing up to 8 years of support, covering both the postdoctoral training and junior faculty stages. The Howard Hughes Medical Institute’s Hanna H. Gray Fellows Program will award up to 15 recipients with $60,000 of salary support and $20,000 in flexible funds paid to their institutions for each of up to 4 years of postdoc training. [Science Insider] Editorial

NEW Novel Concepts in the Biology and Treatment of Metastatic Cancer Conference
November 5-8, 2016
Paphos, Cyprus

NEW Cancer Immunotherapy
November 7-8, 2016
San Francisco, United States

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

NEW Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

NEW Research Associate – Cellular Therapy (California Institute for Biomedical Research)

NEW Director – Immunobiology and Microbial Pathogenesis (The Salk Institute for Biological Studies)

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

Postdoctoral Opportunities – Immunology (Keck School of Medicine)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

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

Professor – Clinical Immunology (Lund University)

Postdoctoral Fellow – Immunology (Icahn School of Medicine at Mount Sinai)

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

Chair – Medical Biology (Masaryk University)

Postdoctoral Fellow Position – Stem Cell Biology & Immunology (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

Postdoctoral Fellow – Genomics and Human Immunity (The Jackson Laboratory)

Postdoctoral Researcher – Translational Immunology (University of Eastern Finland)

Faculty Position – Immunology (Vanderbilt University Medical Center)

Postdoctoral Fellow – Mucosal Immunology (University of Utah)

Postdoctoral Position – Tumor Immunology and T Cell Differentiation (University of Lausanne)

Postdoctoral Research Scientist (National Taiwan University)

Postdoctoral Position – Tumor Immunology (Roswell Park Cancer Institute)

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

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