Immune Regulation News Volume 6.25 | Jul 11 2014

IL-33/ST2 Axis Promotes Mast Cell Survival via BCLXL
In skin-derived human mast cells (MC), researchers found that IL-33 attenuated MC apoptosis without altering proliferation, an effect mediated principally through the antiapoptotic molecule B-cell lymphoma-X large (BCLXL). Murine MC demonstrated a similar mechanism, dependent entirely on ST2. [Proc Natl Acad Sci USA] Abstract

Resolution of Acute Inflammation Bridges the Gap between Innate and Adaptive Immunity
Using the peritoneal cavity investigators found that while innate immune-mediated responses to low-dose zymosan or bacteria resolve within days, these stimuli, but not hyper-inflammatory stimuli trigger a previously overlooked second wave of leukocyte influx into tissues that persists for weeks. [Blood] Abstract

The Skin Immune Atlas: Three-Dimensional Analysis of Cutaneous Leukocyte Subsets by In Vivo Microscopy
Researchers used intravital multiphoton microscopy in transgenic reporter mice in combination with quantitative flow cytometry to generate a 3D immune cell atlas of mouse skin. The 3D location of innate and adaptive immune cells and site-specific differences in the densities of macrophages, T cells and mast cells at four defined sites (ear, back, footpad, tail) is presented. [J Invest Dermatol] Abstract

Immune Suppression via Glucocorticoid-Stimulated Monocytes: A Novel Mechanism To Cope with Inflammation
Scientists found that injection of glucocorticoid-stimulated monocytes (GCsMs) into mice with severe colitis abolished the inflammation and resulted in significant clinical improvement within a few days. T cells recovered from GCsM-treated mice exhibited reduced secretion of proinflammatory cytokines IFN-γ and IL-17. [J Immunol] Abstract

The Catalytic Activity of the MAP Kinase ERK3 Is Required to Sustain CD4⁺CD8⁺ Thymocyte Survival
Given the central role of mitogen-activated protein (MAP) kinases in T cell development, investigators hypothesized that extracellular signal-regulated kinase 3 (ERK3) may regulate thymocyte development. They showed that ERK3 deficiency leads to a 50% reduction in CD4⁺CD8⁺ thymocyte number. [Mol Cell Biol] Abstract

Antitumor Effects of Baculovirus-Infected Dendritic Cells against Human Pancreatic Carcinoma
Scientists examined the antitumor effect of baculovirus-infected dendritic cells (BV-DCs) on human pancreatic cancer cells (AsPC-1). After treatment with BV-infected bone marrow-derived dendritic cells (BMDCs), human pancreatic tumors caused by AsPC-1 cells in a nude mouse model were significantly reduced in size, and the survival of the mice was improved compared with that of non-immature BMDC- and BV-DC-immunized mice. [Gene Ther] Abstract

Neutrophils Contribute to Excess Serum BAFF Levels and Promote CD4⁺ T Cell and B Cell Responses in Lupus-Prone Mice
Researchers aimed to identify factors in autoantibody-mediated autoimmunity that controls the accumulation of spleen resident neutrophils and to determine whether neutrophils contribute to abnormal B cell responses. [PLoS One] Full Article

TRAF3 Regulates Homeostasis of CD8⁺ Central Memory T Cells
Researchers present new findings that reveal differential roles for TNF receptor associated factor 3 (TRAF3) in the regulation of CD4⁺ and CD8⁺ T cells. [PLoS One] Full Article

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Bristol-Myers Squibb Announces Plans for Third Quarter Submission of a Biologics License Application for Opdivo^® (Nivolumab), an Investigational PD-1 Immune Checkpoint Inhibitor, for Previously Treated Advanced Melanoma
Bristol-Myers Squibb Company announced that, following discussions with the U.S. Food and Drug Administration, the company is planning a third quarter submission of a Biologics Licensing Application for Opdivo^® for previously treated advanced melanoma. [Bristol-Myers Squibb Company] Press Release

Histogen Oncology Created to Develop Novel Biologic Cancer Treatments
Histogen Inc. has partnered with Southern California medical device group Wylde, LLC to create Histogen Oncology. This joint venture will focus on the development of unique cell-derived materials for cancer applications. [Histogen Inc.] Press Release

Compugen Discloses Achievement of Milestone in Cancer Immunotherapy Collaboration with Bayer
Compugen Ltd. disclosed that it has achieved the initial milestone in the cancer immunotherapy collaboration it entered last year with Bayer HealthCare. The collaboration provides for the development and commercialization of therapeutic antibodies against two checkpoint protein candidates discovered by Compugen. [Compugen Ltd.] Press Release

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