Immune Regulation News Volume 6.35 | Sep 19 2014

DC Isoketal-Modified Proteins Activate T Cells and Promote Hypertension
The authors describe a pathway in which hypertensive stimuli promote dendritic cell (DC) activation of T cells, ultimately leading to hypertension. Activated DCs promoted T cell, particularly CD8⁺ T cell, proliferation; production of IFN-γ and IL-17A; and hypertension. [J Clin Invest] Full Article | Press Release

Tumor-Secreted miR-214 Induces Regulatory T Cells: A Major Link between Immune Evasion and Tumor Growth
Researchers observed an increased secretion of miR-214 in various types of human cancers and mouse tumor models. In targeted mouse peripheral CD4⁺ T cells, tumor-derived miR-214 efficiently downregulated phosphatase and tensin homolog and promoted regulatory T cell (Treg) expansion. The miR-214-induced Tregs secreted higher levels of IL-10 and promoted tumor growth in nude mice. [Cell Res] Full Article

Anti-CD20 Therapy Induces a Memory Th1 Response through the IFN-γ/IL-12 Axis and Prevents Protumor Regulatory T-Cell Expansion in Mice
Investigators compared tumor immunity in tumor-bearing animals that did or did not receive anti-CD20 treatment. Splenic CD4⁺FoxP3⁺ regulatory T cells (Tregs) expanded substantially in untreated mice that exhibited then a reduced survival, whereas Tregs depletion led to long-term survival of the animals, suggesting the establishment of a Treg-dependent immune-suppressive environment after tumor injection. [Leukemia] Abstract

Specific Roles for Dendritic Cell Subsets during Initiation and Progression of Psoriasis
Scientists investigated the contribution of Langerhans cells (LCs) and plasmacytoid dendritic cells (pDCs) in psoriasis. Depletion of pDCs in a psoriasis mouse model prior to psoriasis induction resulted in a milder phenotype, whereas depletion during active disease had no effect. In contrast, while depletion of Langerin-expressing APCs before disease onset had no effect, depletion from diseased mice aggravated psoriasis symptoms. [EMBO Mol Med] Full Article | Press Release

Dual-Specificity Phosphatase 6 Regulates CD4⁺ T-Cell Functions and Restrains Spontaneous Colitis in IL-10-Deficient Mice
Investigators studied the role of dual-specificity phosphatase 6 (DUSP6) in CD4⁺ T-cell function, differentiation, and inflammatory profile in the colon. Upon T-cell receptor stimulation, DUSP6 knockout CD4⁺ T cells showed increased extracellular signal-regulated kinases 1 and 2 activation, proliferation, T helper 1 differentiation, and interferon-γ production, as well as a marked decrease in survival, interleukin- 17A secretion, and regulatory T-cell function. [Mucosal Immunol] Abstract

IL-33 Is an Unconventional Alarmin that Stimulates IL-2 Secretion by Dendritic Cells to Selectively Expand IL-33R/ST2⁺ Regulatory T Cells
Researchers identified a feedback loop in which conventional mouse CD11c⁺ dendritic cells stimulated by IL-33 secrete IL-2 to selectively expand IL-33R(ST2⁺)-suppressive CD4⁺Foxp3⁺ regulatory T cells. [J Immunol] Abstract

Anti-Metastatic Immunotherapy Based on Mucosal Administration of Flagellin and Immunomodulatory P10
Scientists show that an immunotherapeutic approach based on the use of the Toll-like receptor-5 ligand flagellin combined with the major histocompatibility complex class II-restricted P10 peptide reduced the number of lung metastasis in a murine melanoma model. Lung macrophages were polarized towards a M1 phenotype, lymph node cells, and splenocytes secreted higher interleukin-12p40 and interferon-γ levels when re-stimulated with tumor antigens. [Immunol Cell Biol] Abstract

Attenuation of Airway Inflammation by Simvastatin and the Implications for Asthma Treatment: Is the Jury Still Out?
The administration of simvastatin decreased the airway responsiveness, the number of airway inflammatory cells, and the interleukin (IL)-4, IL-5 and IL-13 concentrations in bronchoalveolar lavage fluid compared with vehicle-treated mice. [Exp Mol Med] Full Article

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Emerging Functions of the Unfolded Protein Response in Immunity
In some types of cells of the immune system, such as dendritic cells and B cells, particular sensors that detect the unfolded protein response (UPR) seem to be constitutively active in the absence of induction of the traditional UPR gene program and are necessary for antigen presentation and immunoglobulin synthesis. The authors summarize these emerging noncanonical functions of the UPR in immunity. [Nat Immunol] Abstract

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Sutro Biopharma and Merck KGaA of Darmstadt, Germany, to Partner on Development of Antibody Drug Conjugates
Sutro Biopharma and the biopharmaceutical division of Merck KGaA, Darmstadt, Germany, announced a collaboration and license agreement to develop antibody drug conjugates. The antibody is thought to specifically target and deliver the cytotoxic drug to the cancer cells. [Sutro Biopharma] Press Release

ImaginAb Expands ImmunoPET Pipeline to Include CD4⁺ T-Cell Imaging
ImaginAb, Inc. announced that it has entered into an exclusive technology development partnership with Novotectid GmbH for the development of antibody-based imaging agents to image CD4⁺ positive immune T cells. [ImaginAb, Inc.] Press Release

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European Medicines Agency (European Union)

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Therapeutic Goods Administration (Australia)

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NEW Postdoctoral Researcher – Immune Response to Cancer (INSERM)

Postdoctoral Position – Immunology (Western New England University)

Research Scientist – Immunology (Institute of Virology and Immunology)

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 )

Assistant Professor – Immunology (Yale University)

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

PhD Studentship – Cancer Immunology (Cardiff 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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