Immune Regulation News Volume 5.40 | Oct 18 2013

Smurf2 Suppresses B-Cell Proliferation and Lymphomagenesis by Mediating Ubiquitination and Degradation of YY1
Researchers showed that Smurf2 mediates ubiquitination and degradation of YY1, a key germinal center transcription factor. Smurf2 deficiency enhances YY1-mediated transactivation of c-Myc and B-cell proliferation. [Nat Commun] Abstract

Exocytosis Acts as a Modulator of the ILT4-Mediated Inhibition of Neutrophil Functions
Scientists showed that primary human neutrophils expressed immunoglobulin-like transcript 4 (ILT4) inhibitory receptor and that this expression was induced during differentiation of the myelomonoblast PLB-985 cell line into “neutrophil-like” cells. Functional assays indicated that human leukocyte antigen G, the preferred ligand of ILT4, inhibited the phagocytic function of neutrophils. [Proc Natl Acad Sci USA] Abstract

CX₃CR1⁺ Cells Facilitate the Activation of CD4 T Cells in the Colonic Lamina Propria during Antigen-Driven Colitis
To investigate whether CX₃CR1⁺ phagocytes communicate with CD4 T cells during the development of transfer colitis, the authors established an antigen-driven colitis model induced by the adoptive transfer of DsRed OT-II cells in CX₃CR1^GFP/+ × RAG^−/− recipients challenged with Escherichia coli expressing ovalbumin fused to a cyan fluorescent protein. [Mucosal Immunol] Abstract

Distinct Temporal Patterns of T Cell Receptor Signaling during Positive versus Negative Selection In Situ
In vitro studies indicate that peptide ligands that induce positive selection stimulate a low, but sustained, pattern of T cell receptor (TCR) signaling; however, the temporal pattern of TCR signaling in MHC class I-restricted thymocytes in the thymus, under conditions that support positive selection, is unknown. Researchers addressed this question by examining intracellular Ca²⁺ dynamics and migratory changes in thymocytes undergoing positive and negative selection in thymic slices. [Sci Sig] Abstract

Particle Shape Dependence of CD8+ T Cell Activation by Artificial Antigen Presenting Cells
The ellipsoidal biomimetic antigen presenting cells (aAPCs) with high-aspect ratios showed significantly enhanced in vitro and in vivo activity above spherical aAPCs with particle volume and antigen content held constant. Confocal imaging indicates that CD8+ T cells preferentially migrate to and are activated by interaction with the long axis of the aAPC. [Biomaterials] Abstract | Press Release

IL-32-PAR2 Axis Is an Innate Immunity Sensor Providing Alternative Signaling for Lipopolysaccharide-TRIF Axis
The authors found that interleukin (IL)-32γ upregulated serine protease activity of proteinase-3 (PR3), in turn triggering protease-activated receptor 2 (PAR2) signaling. Interestingly, silencing of PR3 or PAR2 using siRNA markedly diminished IL-32γ-induced TNFα and IFN-β mRNA expression. [Sci Rep] Full Article

IL-21 Modulates Activation of NKT Cells in Patients with Stage IV Malignant Melanoma
In a phase IIa trial of patients with metastatic melanoma, investigators analyzed the frequency and function of natural killer T (NKT) cells in patients receiving recombinant IL-21 (rIL-21). NKT cells were present at a low frequency, but their levels were relatively stable in patients administered rIL-21. [Clin & Transl Immunol] Full Article

Cofilin: A Redox Sensitive Mediator of Actin Dynamics during T-Cell Activation and Migration
Cofilin is an actin-binding protein that depolymerizes and/or severs actin filaments. This dual function of cofilin makes it one of the major regulators of actin dynamics important for T-cell activation and migration. The activity of cofilin is spatio-temporally regulated. [Immunol Rev] Full Article

Gut T_FH and IgA: Key Players for Regulation of Bacterial Communities and Immune Homeostasis
This review discusses the finely tuned regulatory mechanisms for Immunoglobulin A (IgA) synthesis in germinal centers of Peyer’s patches and emphasize the roles of CD4⁺ T cells for IgA selection and the maintenance of appropriate gut microbial communities required for immune homeostasis. [Immunol Cell Biol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation field.

Kadmon Corporation Announces Development Plans for Selective ROCK 2 Inhibitor, KD025, in Psoriasis, Lupus Nephritis and NASH
Kadmon Corporation, LLC, announced plans for the initiation of three clinical studies of KD025, an orally bioavailable, potent and highly selective inhibitor of ROCK 2 (Rho-associated coiled-coiled kinase 2), in each of three indications: psoriasis, lupus nephritis and non-alcoholic steatohepatitis (NASH). [Kadmon Corporation, LLC] Press Release

The Terry Fox Foundation Tackles “Unmet Cancer Needs” with $13.6 Million for Rare Tumor, Lymphoma and Early-Stage Prostate and Esophageal Cancer Research
Three exemplary Canadian cancer research teams are receiving $13.6 million from the Terry Fox Foundation to conduct cutting-edge research in several areas where there are unmet cancer needs. [The Terry Fox Foundation] Press Release

From our sponsor: Free mouse hematopoietic progenitors wallchart. Request your copy.

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)

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

Postdoctoral Fellow – Anti-Tumor Immunity (H. Lee Moffitt Cancer Center & Research Institute)

Postdoctoral Research Fellow – Immunotherapy (Washington University School of Medicine)

Senior Principal Scientist – Immunology (Johnson & Johnson)

Postdoctoral Fellow – Ripk1 in Innate Immune Responses and Necroptosis (University of Massachusetts Medical School)

PhD Position – T-Lymphocyte Antigen Recognition (Medical University of Vienna)

Research Fellow – Immunology (Queen’s University Belfast)

PhD/Postdoctoral Positions – Quantitative T-Cell Immunology (University of Leeds)

Postdoctoral Fellowship – Immunology (Johns Hopkins University School of Medicine)

PhD Research Position – Molecular and Cellular Mechanisms of Immune Tolerance and Autoimmunity (Weizmann Institute of Science)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Technologist – Cell Culture Media & Matrices (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

Recruit Top Talent: Reach more than 50,000 potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.