Volume 6.33 | Sep 5

Immune Regulation News 6.33 September 5, 2014
Immune Regulation News
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A Local Macrophage Chemokine Network Sustains Protective Tissue-Resident Memory CD4 T Cells
Using parabiotic mice, researchers show that a preexisting pool of CD4 resident memory T (TRM) cells in the genital mucosa was required for full protection from a lethal herpes simplex virus 2 infection. Chemokines secreted by a local network of macrophages maintained vaginal CD4 TRM in memory lymphocyte clusters, independently of circulating memory T cells. [Science] Abstract | Press Release
Free Poster: Quick Reference for Mouse Immune Cell Frequencies and Percentages
PUBLICATIONS (Ranked by impact factor of the journal)
Sequential Transcriptional Changes Dictate Safe and Effective Antigen-Specific Immunotherapy
Optimization of dosing strategy is critical for effective modulation of pathogenic ​CD4+ T-cell activity. Investigators report that dose escalation is imperative for safe, subcutaneous delivery of the high self-antigen doses required for effective tolerance induction, and elicits anergic ​interleukin-10-secreting regulatory ​CD4+ T cells. [Nat Commun] Full Article | Press Release

TSC1 Controls Macrophage Polarization to Prevent Inflammatory Disease
Investigators show that tuberous sclerosis complex 1 (TSC1) is a critical regulator of M1 and M2 phenotypes of macrophages. Mice with myeloid-specific deletion of TSC1 exhibit enhanced M1 response and spontaneously develop M1-related inflammatory disorders. However, TSC1-deficient mice are highly resistant to M2-polarized allergic asthma. [Nat Commun] Abstract

Interleukin-10+ Regulatory B Cells Arise within Antigen-Experienced CD40+ B Cells to Maintain Tolerance to Islet Autoantigens
Scientists hypothesized that naturally occurring, interleukin-10-producing regulatory B cells maintain tolerance to islet autoantigens, and that hyperglycemic nonobese diabetic mice and type 1 diabetes patients lack these potent negative regulators. [Diabetes] Abstract

IL-23 Activates Innate Lymphoid Cells to Promote Neonatal Intestinal Pathology
Investigators show that interleukin (IL)-23 promotes conversion of embryonic intestinal LinIL-23R+Thy1+ cells into IL-22-producing Thy1+Sca-1hi group 3 innate lymphoid cells in vitro. [Mucosal Immunol] Abstract

The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers
To understand how the Bcl6 transcriptional repressor functions in the immune system, scientists disrupted its RD2 repression domain in mice. Bcl6RD2MUT mice exhibited a complete loss of germinal center formation but retained normal extrafollicular responses. [Cell Rep] Full Article | Graphical Abstract

IL-6 trans-Signaling-Dependent Rapid Development of Cytotoxic CD8+ T Cell Function
During inflammation, mature antigen-presenting dendritic cells instruct naive T cells within lymphoid organs to develop into effector T cells. Researchers report a mechanistically distinct and more rapid process of effector T cell development occurring within 18 hours. Interleukin-6 (IL-6) trans-signaling was required and sufficient for rapid induction of granzyme B expression in CD8+ T cells. [Cell Rep]
Full Article | Graphical Abstract | Press Release

CD4+FoxP3+ Regulatory T Cells Suppress Fatal T Helper 2 Cell Immunity during Pulmonary Fungal Infection
Researchers investigated the role of regulatory T (Treg) cells during experimental murine pulmonary Cryptococcus neoformans infection. In Treg cell-depleted mice, stronger pulmonary allergic inflammation with enhanced mucus production and pronounced eosinophilia, increased IgE production, and elevated fungal lung burden were found. This was accompanied by higher frequencies of GATA-3+ T helper 2 cells with elevated capacity to produce interleukin (IL)-4, IL-5 and IL-13. [Eur J Immunol] Abstract

Activation of CD1d-Restricted Natural Killer T Cells Can Inhibit Cancer Cell Proliferation during Chemotherapy by Promoting the Immune Responses in Murine Mesothelioma
Investigators studied the impact of natural killer T (NKT) cell activation by alpha-galactosylceramide (α-GC) on cancer cell repopulation during chemotherapy in murine mesothelioma. NKT cells specifically recognized α-GC through CD1d resulting in their activation and expansion. [Cancer Immunol Immunother] Abstract

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Free Demo: Isolate Cells in the New 96-Well EasySep™ EasyPlate Magnet
Hydrogels and Scaffolds for Immunomodulation
The authors provide an insight into emerging hydrogel and scaffold based immunomodulatory approaches that continue to demonstrate efficacy against immune associated diseases. [Adv Mater] Abstract

Roles of Tumor Suppressors in Regulating Tumor-Associated Inflammation
The authors review evidence from clinical data sets and mouse model studies demonstrating enhanced inflammation and altered tumor microenvironment upon tumor suppressor inactivation. [Cell Death Differ] Full Article

Visit our reviews page to see a complete list of reviews in the immune regulation research field.
Merck Receives Accelerated Approval of KEYTRUDA® (Pembrolizumab), the First FDA-Approved Anti-PD-1 Therapy
Merck announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA® for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. [Merck & Co., Inc.] Press Release

Ludwig Cancer Research and Cancer Research Institute Collaborate on Evaluation of VentiRx’s Investigational Immunotherapy
Ludwig Cancer Research and the Cancer Research Institute (CRI) announced an agreement with VentiRx Pharmaceuticals Inc. to conduct a clinical trial with motolimod combined with other immunotherapy agents available to Ludwig and CRI through other industry partnerships. [Cancer Research Institute] Press Release

Ascend Biopharmaceuticals Clinical Trial Program Update
Ascend Biopharmaceuticals plans to begin a Phase II clinical trial on ASN-002, an injectable immunotherapy for basal cell carcinoma, by 2015. Ascend has also announced plans to begin a Phase Ib study on a therapeutic cancer vaccine for breast cancer, ASN-004, in the second half of 2015. [Ascend Biopharmaceuticals Ltd.] Press Release

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National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW 3rd Conference of Translational Medicine on the Pathogenesis and Therapy of Immune-Mediated Disease
September 30-October 2, 2014
Milan, Italy

NEW 8th Vaccine & ISV Congress
October 26-28, 2014
Philadelphia, United States

NEW European Society for Medical Oncology (ESMO) Symposium on Immuno-Oncology 2014
November 21-22, 2014
Geneva, Switzerland

Visit our events page to see a complete list of events in the immune regulation community.
NEW Faculty Positions – Cancer Immunotherapy and Tumor Microenvironment (NYU Langone Medical Center)

PhD Position – Anti-Cancer γδT Cells (Free University of Brussels)

Postdoctoral Position – Transplantation Aspects of Hepatocytes Derived from Human Pluripotent Stem Cells (INSERM UMR 1064 )

Research Scientist – Cellular Immunology and Oncology (Trillium Therapeutics Inc.)

Assistant Professor – Immunology (Yale University)

Postdoctoral Fellow – Innate-Adaptive Interface in Autoimmunity (Singapore Immunology Network)

Postdoctoral Position – Macrophages Functions (Cochin Institute)

PhD Studentship – Regulation of Metabolism and Inflammation in Innate Immune Cells (Goethe-University Frankfurt)

PhD Studentship – Cancer Immunology (Cardiff University)

Postdoctoral Position – Human Heart Transplantation Immunology (Columbia University)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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