Immune Regulation News Volume 7.19 | May 29 2015

Stk38 Protein Kinase Preferentially Inhibits TLR9-Activated Inflammatory Responses by Promoting MEKK2 Ubiquitination in Macrophages
Researchers demonstrated that Stk38 negatively regulates TLR9-mediated immune responses in macrophages. Stk38 constitutively associates with ubiquitin E3 ligase Smurf1, and facilitates Smurf1-mediated MEKK2 ubiquitination and degradation. [Nat Commun] Abstract

T Cells Integrate Local and Global Cues to Discriminate between Structurally Similar Antigens
Scientists demonstrated how the IL-2 cytokine, collectively generated by strongly activated T cell clones, can induce weaker T cell clones to proliferate. They identified the PI3K pathway as being critical for integrating the antigen and cytokine responses and for controlling cell-cycle entry. [Cell Rep] Full Article | Graphical Abstract

The Cell-Intrinsic Circadian Clock Is Dispensable for Lymphocyte Differentiation and Function
Using a circadian reporter, scientists observed dynamic regulation of clock activity in lymphocytes. However, its disruption upon conditional Bmal1 ablation did not alter T- or B-cell differentiation or function. [Cell Rep] Full Article | Graphical Abstract

Pilot Study Evaluating Regulatory T Cell–Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model
Scientists report an immunotherapy regimen that combines 1-ethyl-3-(3′-dimethylaminopropyl)-carbodiimide-treated donor lymphoid cell infusion with thymoglobulin, anti-interleukin-6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate model. [Am J Transplant] Abstract

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles
Immunization in the presence of tetraphenyl chlorine disulphonate (TPCS2a) significantly increased activation of CD8 T cells compared with immunization without TPCS2a and as measured by CD8 T cell proliferation, production of proinflammatory IFN-γ, TNF-α, and IL-2, and prevention of tumor growth. [J Immunol] Abstract

TGF-β Downregulates KLRG1 Expression in Mouse and Human CD8⁺ T Cells
Investigators demonstrated that killer cell lectin-like receptor G1 (KLRG1) and integrin α_E (CD103) expression in CD8⁺ T cells from untreated and virus-infected mice are mutually exclusive. Inverse correlation of KLRG1 and CD103 expression was also found in human CD8⁺ T cells infiltrating hepatocellular carcinomas. [Eur J Immunol] Abstract

Control of IFN-γ Production and Regulatory Function by the Inducible Nuclear Protein IκB-ζ in T Cells
The authors observed increased numbers of peripheral effector/memory CD4⁺ cells and IFN-γ-producing CD4⁺ cells in three-week-old mice. They found that IκB-ζ can be up-regulated by TGF-β1 in naïve CD4⁺ T cells and that it negatively regulates IFN-γ expression. [J Leukoc Biol] Abstract

Enhanced T Cell Activation and Differentiation in Lymphocytes from Transgenic Mice Expressing Ubiquitination-Resistant 2KR LAT Molecules
To investigate the role of linker for activation of T cells (LAT) ubiquitination in vivo, scientists generated transgenic mice expressing WT and ubiquitin-defective substitution of LAT lysines with arginines (2KR LAT). Upon T cell Receptor stimulation of T cells from these mice, proximal signaling and cytokine production was elevated in 2KR versus WT LAT mice. [Gene Ther] Abstract

In Vivo Monitoring of Activated Macrophages and Neutrophils in Response to Ischemic Osteonecrosis in a Mouse Model
With the recent development of real-time imaging probes for neutrophils and macrophages, researchers investigated the kinetic immune cell response in a mouse model of ischemic osteonecrosis. [J Orthop Res] Abstract

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Regulation of the Neurodegenerative Process Associated to Parkinson’s Disease by CD4⁺ T-Cells
The authors analyze the pathogenic role of inflammatory phenotypes and the beneficial role of anti-inflammatory phenotypes of encephalitogenic CD4⁺ T-cells involved in the physiopathology of Parkinson’s disease. [J Neuroimmune Pharmacol] Abstract

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Ibrutinib (IMBRUVICA^®) in Combination with Anti-PD-L1 Antibody (MEDI4736) Study Commences for Patients with Two Relapsed/Refractory Blood Cancers
Pharmacyclics, Inc. announced the initiation of PCYC-1136-CA, a multi-center study that will investigate the use of ibrutinib (IMBRUVICA^®) in combination with MEDI4736, an investigational anti-PD-L1 immune checkpoint inhibitor being developed by AstraZeneca. [Pharmacyclics, Inc. (PR Newswire Association LLC)] Press Release

Medifocus Inc. Announces Option Agreement with Major Academic Medical Center to License Technology to Develop Heat Activated and Tumor Targeted Immunotherapy
Medifocus, Inc. announced that the company has entered into an option agreement with Duke University regarding heat-activated and tumor targeted Immunotherapy. [Medifocus, Inc.] Press Release

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Therapeutic Goods Administration (Australia)

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Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Head Stem Cells Immunotherapies Service Lab (NHS Blood and Transplant)

Postdoctoral Fellow – Immune Reconstitution in Hematopoietic Stem Cell Transplantation (Stanford University)

Process Facilitator (Opexa Therapeutics)

Postdoctoral Fellow – Immune Tolerance (Stanford University)

Postdoctoral Researcher – Autoimmunity and Antibody Engineering (Karolinska Institutet)

Project Leader – Immunology (Cellectis Inc.)

Postdoctoral Fellow – Immunology (Boston Children’s Hospital)

Postdoctoral Fellow – Genomic and Immunogenomic Aspects of Lymphomas (University of Chicago)

Principal Scientist – Antibody Discovery, Biologics Research (Janssen Research & Development LLC.)

Postdoctoral Fellow – Immunopathogenesis of Multiple Sclerosis (University of Iowa)

Senior Scientist – Immunology (National Institute of Immunology)

Assistant Professor – Immunology (Northwestern University)

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