Volume 5.18 | May 17

Immune Regulation News 5.18 May 17, 2013
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Natural and Inducible TH17 Cells Are Regulated Differently by Akt and mTOR Pathways
The authors demonstrated that the serine/threonine kinase Akt has a critical role in regulating natural T helper 17 (nTH17) cell development. Although Akt and the downstream mTORC1-ARNT-HIFα axis were required for generation of inducible TH17 cells, nTH17 cells developed independently of mTORC1. [Nat Immunol]
Abstract | Press Release

A New System for High-Throughput Cell Isolation Directly from Whole Blood
PUBLICATIONS (Ranked by impact factor of the journal)

VAMP7 Controls T Cell Activation by Regulating the Recruitment and Phosphorylation of Vesicular Lat at TCR-Activation Sites
Investigators found, by silencing approaches and genetically modified mice, that the vesicular SNARE VAMP7 was required for the recruitment of Lat-containing vesicles to T cell antigen receptor (TCR)-activation sites. [Nat Immunol] Abstract

Real-Time In Vivo Analysis of T Cell Activation in the Central Nervous System Using a Genetically Encoded Calcium Indicator
To study T cell activation in vivo in real time, researchers introduced a newly developed fluorescence resonance energy transfer-based, genetically encoded calcium indicator into autoantigen-specific and non-autoantigen-specific CD4+ T cells. [Nat Med] Abstract

EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation
Investigators found that EZH2 deletion or pharmacologic inhibition suppresses germinal cell (GC) formation and functions. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B cell differentiation. [Cancer Cell]
Abstract | Press Release

Generation of Functional Thymic Epithelium from Human Embryonic Stem Cells that Supports Host T Cell Development
Researchers describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into thymic epithelial progenitors (TEPs) by precise regulation of TGFβ, BMP4, RA, Wnt, Shh, and FGF signaling. The hESC-derived TEPs further mature into functional thymic epithelial cells that support T cell development upon transplantation into thymus-deficient mice. [Cell Stem Cell]
Abstract | Graphical Abstract | Press Release

An Inherently Bifunctional Subset of Foxp3+ T Helper Cells Is Controlled by the Transcription Factor Eos
At sites of inflammation, certain regulatory T cells can undergo rapid reprogramming into helper-like cells without loss of the transcription factor Foxp3. Scientists showed that reprogramming is controlled by downregulation of the transcription factor Eos, an obligate corepressor for Foxp3. [Immunity]
Abstract | Graphical Abstract

Cognate Antigen Directs CD8+ T Cell Migration to Vascularized Transplants
The prevailing view is that key steps involved in T cell migration – integrin-mediated firm adhesion followed by transendothelial migration – are dependent on the activation of Gαi-coupled chemokine receptors on T cells. In contrast to this view, researchers demonstrated in vivo that cognate antigen was necessary for the firm adhesion and transendothelial migration of CD8+ effector T cells specific to graft antigens and that both steps occurred independent of Gαi signaling. [J Clin Invest] Full Article

Primary Tumors Modulate Innate Immune Signaling to Create Pre-Metastatic Vascular Hyperpermeability Foci
The authors showed that MD-2, a coreceptor for Toll-like receptor 4 that has a key role in the innate immune response, triggers the formation of regions of hyperpermeability in mice by upregulating C-C chemokine receptor type 2 expression. [Nat Commun] Full Article

Identification of CD3+CD4CD8T Cells as Potential Regulatory Cells in an Experimental Murine Model of Graft vs. Host Skin Disease (GvHD)
The authors developed K14-mOVA transgenic (Tg) mice that express membrane-associated ovalbumin (mOVA) under the control of a K14 promoter as well as double Tg mice by crossing them with OT-I mice that have a T cell receptor recognizing OVA peptide. When injected with CD8+ OT-I cells, K14-mOVATg mice develop GvHD, whereas double Tg mice are protected. [J Invest Dermatol] Abstract

Markers of Nonselective and Specific NK Cell Activation
NK cells undergo two distinct phases of activation during murine CMV infection: a nonselective phase mediated by proinflammatory cytokines and a specific phase driven by signaling through Ly49H, an NK cell activation receptor that recognizes infected cells. Investigators sought to delineate cell surface markers that could distinguish NK cells that had been activated nonselectively from those that had been specifically activated through NK cell receptors. [J Immunol] Abstract

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Regulation of Innate and Adaptive Immunity by Notch
Researchers summarize the current status of immune regulation by Notch. A better understanding of Notch function in both innate and adaptive immunity will hopefully provide multiple avenues for therapeutic intervention in disease. [Nat Rev Immunol] Abstract

The Innate Immune Response during Liver Inflammation and Metabolic Disease
Innate immune cells recognize cell damage or pathogen invasion with intracellular or surface-expressed pattern recognition receptors (PRRs). Activated PRRs subsequently initiate signaling cascades that trigger the release of factors promoting the inflammatory response. Because the liver is a site where foreign antigens from the gastrointestinal tract encounter the immune system, it is particularly enriched with innate immune cells. [Trends Immunol] Abstract

Induced and Natural Regulatory T Cells in the Development of Inflammatory Bowel Disease
The authors summarize the development and function of regulatory T (Treg) cells and how their regulatory mechanisms may fail, leading to a loss of mucosal tolerance. They discuss both animal models and studies of patients with inflammatory bowel disease (IBD) suggesting Treg cell involvement in IBD and consider how Treg cells may be used in future therapies. [Inflamm Bowel Dis] Abstract

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ImmunoCellular Therapeutics Announces Issuance of Key Patent Covering ICT-107 Cancer Vaccine Target
ImmunoCellular Therapeutics, Ltd. announced that the US Patent and Trademark Office has issued a patent covering methods of use of interleukin 13-receptor alpha 2 protein (IL-13Rα2) in cancer immunotherapy. IL-13 is an immune regulatory cytokine and IL-13Rα2 is highly and specifically expressed in glioblastoma, ovarian and other solid tumors, but not in normal tissue. [ImmunoCellular Therapeutics, Ltd.] Press Release

Yale Cancer Center Carves New Path in Immunotherapy

Cancer immunotherapy is showing promise in treating patients with a variety of advanced, metastatic tumors, as evidenced by two newly unveiled studies from Yale Cancer Center. [Yale University] Press Release

AbbVie and Galapagos Extend GLPG0634 Collaboration to Include Crohn’s Disease
Galapagos NV and AbbVie announced an extension of their GLPG0634 clinical development collaboration to include Crohn’s disease. Galapagos will fund and complete a Phase II program in Crohn’s disease, which is designed to facilitate rapid progression into Phase III. [AbbVie Inc.] Press Release

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Therapeutic Goods Administration (Australia)


NEW Antibody Congress Asia 2013
June 17-20, 2013
Singapore, Singapore

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


NEW Research Associate – NeuroOncology (University of Chicago – Department of Surgery)
PhD Studentship – Role of Epigenetic Regulators in Control of Immunity and Inflammation (King’s College London)

Postdoctoral Researcher – Innate Immunity (Massachusetts General Hospital / Harvard Medical School)

PhD Studentship – The Role of Adipocyte Progenitor Cells during Immune Responses (University of Birmingham)

Postdoctoral Fellowship – Tumor Immunology (Northwestern University – Robert H Lurie Comprehensive Cancer Center)

Postdoctoral Fellow – Immunological Pathways in Human Inflammatory Bowel Disease (Yale University – School of Medicine)

PhD Studentship – Mucosal Immunology (KU Leuven Translational Research Center for Gastrointestinal Disorders)

Postdoctoral Position – Immunology (INSERM 1020)

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