Immune Regulation News Volume 6.34 | Sep 12 2014

CD8αα⁺ Innate-Type Lymphocytes in the Intestinal Epithelium Mediate Mucosal Immunity
Researchers describe an innate lymphocyte population, iCD8α cells, characterized by expression of CD8α homodimers. iCD8α cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. [Immunity] Abstract | Graphical Abstract

Resident ​CD4⁺ T Cells Accumulate in Lymphoid Organs after Prolonged Antigen Exposure
Investigators analyzed the migration of effector/memory ​CD4⁺ T cells by long-term in vivo cell tracking. They identified a resident population of antigen-experienced ​CD4⁺ T cells that resides in lymph nodes and Peyer’s patches without circulation or proliferation. [Nat Commun] Abstract

Homeostatic IL-23 Receptor Signaling Limits Th17 Response through IL-22-Mediated Containment of Commensal Microbiota
Scientists demonstrate that the IL-23 pathway dynamically regulates the abundance of certain commensals and maintains barrier function. Through induction of IL-22, IL-23 contributes to barrier repair, and through induction of the Th17 response, it aims to neutralize escaped commensal microbes. [Proc Natl Acad Sci USA] Abstract

Polycomb-Mediated Loss of MicroRNA Let-7c Determines Inflammatory Macrophage Polarization via PAK1-Dependent NF-κB Pathway
Scientists show that inflammatory stimuli induced p21-activated kinase 1 (PAK1) overexpression in human and murine macrophages. Elevated expression of PAK1 contributed to macrophage M1 polarization and lipopolysaccharide-induced endotoxin shock. [Cell Death Differ] Abstract

Dendritic Cell CD83 Homotypic Interactions Regulate Inflammation and Promote Mucosal Homeostasis
Investigators show that CD83, a highly regulated dendritic cell (DC) surface protein, modulates the immune response to prevent colitis. Mice with a conditional knockout of CD83 in DCs developed exacerbated colitis following dextran sodium sulfate challenge, whereas mucosal overexpression of CD83 inhibited DC inflammatory response and protected against colitis. [Mucosal Immunol] Full Article

Ectosomes Released by Platelets Induce Differentiation of CD4⁺ T Cells into T Regulatory Cells
The authors investigated the effects mediated by platelet-derived ectosomes (PLT-Ecto) on CD4⁺ T cells. Exposure of activated CD4⁺ T cells to PLT-Ecto decreased their release of IFNγ, TNFα and IL-6, and increased the production of TGF-β1. Concomitantly, PLT-Ecto-exposed CD4⁺ T cells displayed increased frequencies of CD25^highFoxp3⁺ cells. [Thromb Haemost] Abstract | Download Full Article

Ligation of TLR5 Promotes Myeloid Cell Infiltration and Differentiation into Mature Osteoclasts in Rheumatoid Arthritis and Experimental Arthritis
Researchers examined the impact of TLR5 ligation in rheumatoid arthritis (RA) and experimental arthritis pathology. Studies were conducted to investigate the role of TLR5 ligation on RA and mouse myeloid cell chemotaxis or osteoclast formation, and in addition, to uncover the significance of TNF-α function in TLR5-mediated pathogenesis. [J Immunol] Abstract | Press Release

Restriction of IL-22-Producing T Cell Responses and Differential Regulation of Regulatory T Cell Compartments by Zinc Finger Transcription Factor Ikaros
Scientists show that mice with targeted deletion of the fourth DNA-binding zinc finger of the transcription factor Ikaros had increased IL-22-producing, but not IL-17-producing, CD4⁺ T cells in the gut. Despite an intact in vivo thymic-derived regulatory T cell (Treg) compartment in these Ikaros-mutant mice, TGF-β, a cytokine well known for induction of Tregs, failed to induce Foxp3 expression in Ikaros-mutant CD4⁺ T cells in vitro and, instead, promoted IL-22. [J Immunol] Abstract

Induction of Suppressive Allogeneic Regulatory T-Cells via Rabbit-ATG during Homeostatic Proliferation in Rat Kidney Transplantation
Experimental studies have shown that rabbit antithymocyte polyclonal globulin (ATG) can expand human CD4⁺CD25⁺⁺Foxp3⁺ cells. Researchers investigated the major biological effects of a self-manufactured rabbit polyclonal anti-rat thymoglobulin in vitro, as well as its effects on different peripheral T cell subsets. [Transpl Int] Abstract

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Altor BioScience and Shenzhen Beike Biotechnology Announce License Agreement for Immunotherapeutic ALT-803 in China
Altor BioScience Corporation and Shenzhen Beike Biotechnology Co., Ltd. announced that they have entered into a license agreement to develop and commercialize ALT-803, Altor’s proprietary Interleukin-15 based superagonist complex, in China. [Altor BioScience Corporation] Press Release

Initiation of Phase III IMPALA Study with Immunotherapy MGN1703 in Colorectal Cancer
MOLOGEN AG has enrolled the first patient in the international IMPALA study. Primary objective of the Phase III pivotal trial is to prove that a switch maintenance therapy with the cancer immunotherapy MGN1703 leads to an increased overall survival in patients with metastatic colorectal carcinoma. [MOLOGEN AG] Press Release

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