Volume 6.41 | Oct 31

Immune Regulation News 6.41 October 31, 2014
Immune Regulation News
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CEACAM1 Regulates TIM-3-Mediated Tolerance and Exhaustion
In a mouse adoptive transfer colitis model, carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1)-deficient T cells are hyper-inflammatory with reduced cell surface expression of T-cell immunoglobulin domain and mucin domain-3 (TIM-3) and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumor environment, CEACAM1 and TIM-3 mark exhausted T cells. [Nature] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Conditional Density-Based Analysis of T Cell Signaling in Single-Cell Data
In comparing signaling between naïve and antigen-exposed CD4+ T-lymphocytes, scientists found that although these two cell subtypes had similarly-wired networks, naïve cells transmitted more information along a key signaling cascade than did antigen-exposed cells. [Science] Abstract

Loss of ​Beta2-Integrin-Mediated Cytoskeletal Linkage Reprograms Dendritic Cells to a Mature Migratory Phenotype
Researchers show that loss of the interaction between beta2-integrins and ​kindlin-3 abolishes the actin-linkage of integrins and the ​GM-CSF receptor in dendritic cells. This leads to increased ​GM-CSF receptor/​Syk signaling, and to the induction of a transcriptional program characteristic of mature, migratory dendritic cells, accumulation of migratory dendritic cells in lymphoid organs, and increased Th1 immune responses in vivo. [Nat Commun] Abstract

Distinct Macrophage Lineages Contribute to Disparate Patterns of Cardiac Recovery and Remodeling in the Neonatal and Adult Heart
Investigators hypothesized that unrecognized differences in macrophage composition is a key determinant of cardiac tissue repair. Using a genetic model of cardiomyocyte ablation, they demonstrate that neonatal mice expand a population of embryonic-derived resident cardiac macrophages, which generate minimal inflammation and promote cardiac recovery through cardiomyocyte proliferation and angiogenesis. [Proc Natl Acad Sci USA] Abstract | Press Release

Insulin-Like Growth Factor-1 Stimulates Regulatory T Cells and Suppresses Autoimmune Disease
Researchers show that recombinant human insulin-like growth factor-1 stimulates proliferation of both human and mouse regulatory T cells in vitro and when delivered systemically via continuous minipump, it halts autoimmune disease progression in mouse models of type 1 diabetes and multiple sclerosis in vivo. [EMBO Mol Med] Full Article | Press Release

Protein Kinase D2 Is a Digital Amplifier of T Cell Receptor-Stimulated Diacylglycerol Signaling in Naïve CD8+ T Cells
Investigators quantified the activation of protein kinase D2 at the single-cell level and found that this kinase acts as a sensitive digital amplifier of T cell receptor (TCR) engagement, enabling CD8+ T cells to match the production of inflammatory cytokines to the quality and quantity of TCR ligands. [Sci Signal] Abstract

Helping Themselves: Optimal Virus-Specific CD4 T Cell Responses Require Help via CD4 T Cell Licensing of Dendritic Cells
Researchers show that activation of adoptively transferred helper T cells during primary influenza A virus (IAV) infection enhances both the magnitude and functional breadth of endogenous primary IAV-specific CD4+ T cell responses. This enhancement was dependent on CD154-CD40-dependent dendritic cell licensing and resulted in a greater recall capacity of IAV-specific CD4+ and CD8+ T memory responses after heterologous IAV infection. [J Immunol] Abstract

Foxp3+ Regulatory T Cells Ensure B Lymphopoiesis by Inhibiting the Granulopoietic Activity of Effector T Cells in Mouse Bone Marrow
Among cytokines enriched in the bone marrow of scurfy mice, IFN-γ affected only B lymphopoiesis, but GM-CSF, TNF, and IL-6 collectively promoted granulopoiesis at the expense of B lymphopoiesis. Regulatory T cells ensured B lymphopoiesis by reducing the production of these cytokines by effector T cells, but not by directly affecting B lymphopoiesis. [Eur J Immunol] Abstract

Toll-Like Receptor Agonists Shape the Immune Responses to a Mannose Receptor-Targeted Cancer Vaccine
Scientists postulated that agents that influenced the mannose receptor (MR) expression level, and the activation and migration status of MR-expressing antigen presenting cells, would modulate immune responses to MR-targeted vaccines. They investigated the effect of clinically used adjuvants in human MR transgenic mice immunized with an MR-targeting cancer vaccine composed of the human anti-MR monoclonal antibody B11 fused with the oncofetal protein, human chorionic gonadotropin beta chain, and referred to as B11-hCGβ. [Cell Mol Immunol] Abstract

Bacterial Capsular Polysaccharide Prevents the Onset of Asthma Through T cell Activation
The authors report that direct treatment of mice with PSA generates protection from asthma, and this effect can be given to a naïve recipient by adoptive transfer of CD4+ T cells from PSA-exposed mice. They found that these PSA-induced T cells are not canonical FoxP3+ regulatory T cells, but that they potently inhibit both Th1 and Th2 models of asthma in an IL-10-dependent fashion. [Glycobiology] Abstract

Neuropilin-1 Expression Is Induced on Tolerant Self-Reactive CD8+ T Cells but Is Dispensable for the Tolerant Phenotype
Scientists discovered that, in addition to other known regulatory receptors, tolerant self-reactive CD8+ T cells distinctly expressed the surface receptor neuropilin-1 (Nrp1). Nrp1 was highly induced in response to self-antigen, but only modestly when the same antigen was encountered under immune conditions, suggesting a possible mechanistic link to T cell tolerance. [PLoS One] Full Article

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Innate Lymphoid Cells in the Skin
The author reviews recent studies delineating the roles of innate lymphoid cells in the pathogenesis of multiple inflammatory skin disorders and their unique effector functions. [J Invest Dermatol] Abstract

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UTHealth Research Shows Mushroom Extract, AHCC, Helpful in Treating HPV
A Japanese mushroom extract appears to be effective for the eradication of human papillomavirus (HPV), according to a pilot clinical trial at The University of Texas Health Science Center at Houston (UTHealth) Medical School. [Press release from The University of Texas Health Science Center at Houston discussing research presented at the 11th International Conference of the Society for Integrative Oncology (SIO), Houston ] Press Release

Advances in Graves’ Disease, Including a New Mouse Model
A unique mouse model of Graves’ disease, an autoimmune disorder that causes hyperthyroidism, and new research findings that may help improve the treatment of Graves’ disease will be highlighted in oral and poster presentations. [Press release from the American Thyroid Association (Newswise, Inc.) discussing research to be presented at the 84th Annual Meeting of the American Thyroid Association (ATA), Coronado] Press Release

Compugen Discloses Successful Validation Results for Novel B7/CD28-Like Cancer Immunotherapy Target Candidate
Compugen Ltd. disclosed successful experimental data for CGEN-15027, a Compugen-discovered immune checkpoint target candidate. The experimental results include its expression in the cancer microenvironment, both on cancer cells derived from lung, breast, and liver cancer patients, and on tumor infiltrating immune cells. [Compugen Ltd.] Press Release

Scripps Research Institute MS Drug Candidate also Shows Promise for Ulcerative Colitis
Positive new clinical data were released on a drug candidate for ulcerative colitis that was first discovered and synthesized at The Scripps Research Institute. [The Scripps Research Institute] Press Release

TxCell Achieves Positive Results for Col-Treg in a Model of Autoimmune Uveitis
TxCell SA announced that TxCell researchers have achieved positive results for Col-Treg, its second product candidate from its ASTrIA platform, in a model of autoimmune uveitis. [TxCell SA] Press Release

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NRC and AvidBiologics Progress New Treatments to Seek and Destroy Cancer Cells
AvidBiologics Inc. and the National Research Council of Canada (NRC) are collaborating on one of the most promising advances in the fight against cancer: antibody-drug conjugates (ADCs). Recently signed research and licensing agreements will enable both organizations to continue developing a series of ADCs targeting breast, lung, and head-and-neck cancers. [National Research Council of Canada] Press Release

Xencor Renegotiates XmAb®5871 Agreement with Amgen; Regains All Rights and Plans Clinical Development in Rare Autoimmune Disease
Xencor, Inc. announced that it has regained all development and commercial rights to XmAb®5871 by seeking and obtaining a termination of the prior option and collaboration agreement and executing a new right-of-first-negotiation agreement with Amgen. [Xencor, Inc.] Press Release
National Institutes of Health (United States)

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)
NEW Federation of African Immunological Societies (FAIS): 9th African Immunology Conference
November 3-December 4, 2014
Nairobi, Kenya

NEW Advances in Cancer Immunotherapy™
December 5, 2014
Tampa, United States

Visit our events page to see a complete list of events in the immune regulation community.
NEW Postdoctoral Research Fellow – Mucosal Immune System in Chronic and Infectious Disease (Griffith Health Institute)

NEW Postdoctoral Research Fellow – Immune Responses to HSV (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Genetic and Epigenetic Regulatory Networks in Protective Immune Responses (Washington University School of Medicine)

Postdoctoral Fellowship – Development of Autoimmunity and Cancer (Mount Sinai Medical Center)

Postdoctoral Researcher – Immune Response to Cancer (INSERM)

Postdoctoral Position – Immunology (Western New England University)

Faculty Positions – Cancer Immunotherapy and Tumor Microenvironment (NYU Langone Medical Center)

Postdoctoral Position – Transplantation Aspects of Hepatocytes Derived from Human Pluripotent Stem Cells (INSERM UMR 1064)

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.)

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