Volume 5.43 | Nov 8

Immune Regulation News 5.43 November 8, 2013
Pulmonary Cell News
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Immunosuppressive CD71+ Erythroid Cells Compromise Neonatal Host Defense against Infection
Scientists showed that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. [Nature] Abstract | Press Release
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TH17 Cell Differentiation Is Regulated by the Circadian Clock
Scientists showed that the transcription factor NFIL3 suppresses TH17 cell development by directly binding and repressing the Rorγt promoter. NFIL3 links TH17 cell development to the circadian clock network through the transcription factor REV-ERBα. [Science] Abstract | Press Release

The Mechanism of Anti-CD20-Mediated B Cell Depletion Revealed by Intravital Imaging
The authors found that the liver is a major site for B cell depletion and that recirculation accounts for the decrease in B cell numbers observed in secondary lymphoid organs. Using intravital imaging, they established that, upon anti-CD20 treatment, Kupffer cells mediate the abrupt arrest and subsequent engulfment of B cells circulating in the liver sinusoids. [J Clin Invest] Full Article | Press Release

B Cells Are Critical for Autoimmune Pathology in Scurfy Mice
Scientists showed that B cells and the production of autoantibodies plays a major role for skin, liver, lung, and kidney inflammation and therapeutic depletion of B cells resulted in reduced tissue pathology and in prolonged survival. In contrast, the absence of B cells did not impact systemic T-cell activation and hyperreactivity, indicating that autoantibody production by B cells may be a major factor for the autoimmune pathology in mice deficient for regulatory T cells. [Proc Natl Acad Sci USA] Abstract

Targeting PKC in Human T Cells Using Sotrastaurin (AEB071) Preserves Regulatory T Cells and Prevents IL-17 Production
Scientists showed that sotrastaurin inhibited effector T cell responses, whereas the regulatory response was enhanced. Sotrastaurin prevented TCR/CD28-induced T-cell activation and pro-inflammatory cytokine production, but preserved a stable regulatory T-cells phenotype as evidenced by maintenance of suppressive capacity, high Foxp3 and CD25 expression, and lack of IL-17A and IFNγ production. [J Invest Dermatol] Abstract

Myosin-Primed Tolerogenic Dendritic Cells Ameliorate Experimental Autoimmune Myocarditis
Researchers investigated whether tolerogenic dendritic cell therapy in an experimental autoimmune myocarditis mouse model can suppress inflammatory myocarditis, a potential precursor of dilated cardiomyopathy. [Cardiovasc Res] Abstract

Recipient Myeloid-Derived Immunomodulatory Cells Induce PD-1 Ligand-Dependent Donor CD4+Foxp3+ Regulatory T Cell Proliferation and Donor-Recipient Immune Tolerance after Murine Nonmyeloablative Bone Marrow Transplantation
The authors showed previously that nonmyeloablative total lymphoid irradiation/rabbit anti-thymocyte serum conditioning facilitates potent donor-recipient immune tolerance following bone marrow transplantation across MHC barriers via recipient invariant NKT cell-derived IL-4-dependent expansion of donor Foxp3+ naturally occurring regulatory T cells. They now report a more specific mechanism. [J Immunol] Abstract

Development of Virus-Specific CD4+ and CD8+ Regulatory T Cells Induced by Human Herpesvirus-6 Infection
Scientists characterized human herpesvirus 6 (HHV-6)-specific T cells in peripheral blood mononuclear cells from HHV-6-infected donors. Their results showed that HHV-6 infection could induce both CD4+ and CD8+ HHV-6-specific regulatory T cells. [J Virol] Abstract

Prevention of GVHD by Adoptive T Regulatory Therapy Is Associated with Active Repression of Peripheral Blood Toll-Like Receptor-5 mRNA Expression
To investigate potential mechanisms responsible for reduced graft-versus-host disease (GVHD) risk, investigators analyzed peripheral blood mononuclear cell mRNA expression of a tolerance gene set previously identified in operational tolerant kidney transplant recipients, comparing healthy controls to patients who received no natural regulatory T cells (nTregs) or nTregs with and without GVHD. [Biol Blood Marrow Transplant] Abstract

Homogeneous Expansion of Human T-Regulatory Cells via Tumor Necrosis Factor Receptor 2
With the goal of producing homogeneous T-regulatory cells (Tregs), researchers developed a novel expansion protocol targeting tumor necrosis factor receptors (TNFR) on Tregs. In in vitro studies, a TNFR2 agonist was found superior to standard methods in proliferating human Tregs into a phenotypically homogeneous population consisting of 14 cell surface markers. [Sci Rep] Full Article

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Immune Mechanisms in Medium and Large-Vessel Vasculitis
The information exchange between vascular and immune cells and stabilization of the vasculitic process involves members of the Notch receptor and ligand family. Focusing on elements in the tissue context of giant cell arteritis, instead of broadly suppressing host immunity, might enable a more tailored therapeutic approach that avoids unwanted adverse effects of aggressive immunosuppression. [Nat Rev Rheumatol] Abstract

Immunobiology of Mesenchymal Stem Cells
The authors focus on the crosstalk between mesenchymal stem cells and immune responses and their potential clinical applications, especially in inflammatory diseases. [Cell Death Differ] Full Article

Visit our reviews page to see a complete list of reviews in the immune regulation field.
Celldex Therapeutics’ CDX-1127 Well Tolerated and Demonstrates Anti-Tumor Activity in Phase I Dose-Escalation Study
Celldex Therapeutics, Inc. reported data from its ongoing Phase I dose-escalation study of the fully human monoclonal antibody CDX-1127. The results suggest an excellent safety profile and demonstrate clear biologic activity and promising signs of clinical activity in an advanced, refractory patient population. [Press release by Celldex Therapeutics, Inc. discussing research to be presented 2013 Society for Immunotherapy of Cancer (SITC) Annual Meeting, National Harbor] Press Release

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CureVac Collaborates with the Cancer Research Institute and Ludwig Cancer Research to Enable Clinical Testing of Novel Immunotherapy Treatment Options for Cancer
The non-profit Cancer Research Institute and Ludwig Cancer Research, and CureVac announced that they will collaborate to enable clinical testing of novel cancer immunotherapy treatment options. [CureVac GmbH] Press Release

STEMCELL Technologies Receives Government of Canada Support to Develop New Cell Isolation Technology that Will Enable Advancements in the Study of the Immune Response to HIV and the Development of HIV Vaccines
STEMCELL Technologies announced that the National Research Council of Canada Industrial Research Assistance Program will provide up to $1.5 million in financial support for the development of cell isolation technology that will further basic and translational HIV research as well as broader research in infectious disease. [STEMCELL Technologies Inc.] Press Release
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European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW The 53rd Midwinter Conference of Immunologists
January 25-28, 2014
Asilomar, United States

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NEW Postdoctoral Fellowship – Immune Regulation by Extracellular Matrix Proteins (Johns Hopkins University)

NEW PhD Studentship – Systems Biology and Lymphocyte Activation (University of Oxford)

Tenure-Track Faculty Position – Women’s Infectious Disease Research (Washington University School of Medicine)

Research Studentship – Imaging Membrane Lipid in Activating T Cells (King’s College London)

Postdoctoral Position – Lymphocyte Motility (INSERM)

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

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

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

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

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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