Volume 8.17 | May 13

Immune Regulation News 8.17 May 13, 2016
Immune Regulation News
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Gene-Microbiota Interactions Contribute to the Pathogenesis of Inflammatory Bowel Disease
Investigators revealed that outer membrane vesicles require inflammatory bowel disease-associated genes, ATG16L1 and NOD2, to activate a non-canonical autophagy pathway during protection from colitis. ATG16L1-deficient dendritic cells do not induce regulatory T cells to suppress mucosal inflammation. [Science]
Abstract | Press Release
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IgA Production Requires B Cell Interaction with Subepithelial Dendritic Cells in Peyer’s Patches
The authors showed that in mice, activated B cells use the chemokine receptor CCR6 to access the subepithelial dome (SED) of Peyer’s patches (PPs). There, B cells undergo prolonged interactions with SED dendritic cells (DCs). PP IgA class switching requires innate lymphoid cells, which promote lymphotoxin-β receptor-dependent maintenance of DCs. [Science] Abstract

Maternal IgG and IgA Antibodies Dampen Mucosal T Helper Cell Responses in Early Life
Scientists report the surprising observation that mice generate T cell-independent and largely Toll-like receptor (TLR)-dependent IgG2b and IgG3 antibody responses against their gut microbiota. They demonstrated that maternal acquisition of these antibodies dampens mucosal T follicular helper responses and subsequent germinal center B cell responses following birth. [Cell] Abstract | Graphical Abstract | Press Release

BACH2 Regulates CD8+ T Cell Differentiation by Controlling Access of AP-1 Factors to Enhancers
Researchers found that the transcription factor (TF) BACH2 restrains terminal differentiation to enable generation of long-lived memory cells and protective immunity after viral infection. BACH2 was recruited to enhancers, where it limited expression of TCR-driven genes by attenuating the availability of activator protein-1 (AP-1) sites to Jun family signal-dependent TFs. [Nat Immunol] Abstract

Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells
Scientists identified functional mouse and human plasmacytoid dendritic cells (pDCs) in the aortic intima and showed that selective, inducible pDC depletion in mice exacerbates atherosclerosis. Aortic pDCs expressed CCR9 and indoleamine 2,3-dioxygenase 1, an enzyme involved in driving the generation of regulatory T cells. [Cell Metab] Abstract | Graphical Abstract

Combinatorial Targeting of TSLP, IL-25, and IL-33 in Type 2 Cytokine–Driven Inflammation and Fibrosis
Using chronic models of helminth infection and allergic lung inflammation, researchers showed that collective disruption of thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25), and IL-33 signaling suppresses chronic and progressive type 2 cytokine-driven inflammation and fibrosis. [Sci Transl Med] Abstract

CD4+ Th2 Cells Are Directly Regulated by IL-10 During Allergic Airway Inflammation
Researchers demonstrated that interleukin-10 (IL-10) directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. [Mucosal Immunol] Full Article

Oral CD103CD11b+ Classical Dendritic Cells Present Sublingual Antigen and Induce Foxp3+ Regulatory T Cells in Draining Lymph Nodes
A major subset of oral classical dendritic cells with the CD103CD11b+ phenotype showed retinoic acid (RA)-producing activity and converted naive CD4+ T cells to Foxp3+ Treg cells in a transforming growth factor-β- and RA-dependent manner in vitro. [Mucosal Immunol] Abstract

Intralesional Rose Bengal in Melanoma Elicits Tumor Immunity via Activation of Dendritic Cells by the Release of High Mobility Group Box 1
The authors showed a mechanism of tumor-specific immune response induced by intralesional (IL) Rose Bengal (RB). In melanoma-bearing mice, IL RB induced regression of injected tumor and inhibited the growth of bystander lesions mediated by CD8+ T cells. [Oncotarget] Full Article | Press Release

LRRK1 Is Critical in the Regulation of B-Cell Responses and CARMA1-Dependent NF-κB Activation
Scientists discovered a critical function of leucine-rich repeat kinase 1 (LRRK1) in B-cell receptor-mediated immune responses. Lrrk1−/− mice exhibited altered B1a-cell development and basal immunoglobulin production. [Sci Rep] Full Article

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Roles of Regulatory T Cells in Cancer Immunity
The authors address the current understanding of regulatory T cell (Treg)-mediated immune suppressive mechanisms in cancer, the involvement of Tregs in cancer immunotherapy, and strategies for effective and tolerable Treg-targeted therapy. [Int Immunol] Abstract

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Epizyme Announces Collaboration with Lymphoma Study Association to Evaluate Combination of Tazemetostat with R-CHOP in Front-line Non-Hodgkin Lymphoma
Epizyme, Inc. announced that it has entered into a collaboration agreement with the Lymphoma Study Association to investigate the combination of tazemetostat with R-CHOP as a front-line treatment in patients with diffuse large B-cell lymphoma. [Epizyme, Inc.] Press Release

X4 Pharmaceuticals Announces Initiation of Phase I/II Study of X4P-001 in Patients with Advanced Clear Cell Renal Cell Carcinoma
X4 Pharmaceuticals announced dosing of the first patient in a Phase I/II study of X4P-001, the company’s lead CXCR4 inhibitor, in patients with advanced clear cell renal cell carcinoma. [X4 Pharmaceuticals] Press Release

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NEW 2016 World Cancer Congress
October 31-November 3, 2016
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NEW Post Doctoral Research – Fellow Thymic and Immune Regeneration (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Fellow – Immunology (New York University Medical Center)

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.)

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)

PhD Positions – Cancer Research (German Cancer Research Center)

Faculty Positions – Immunology and Host-Microbe Interactions (Ohio State University)

Junior Group Leader – Immunology (Laboratory of Excellence)

Single Cell Immunologist (Berkeley Lights, Inc.)

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

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