Volume 5.00 | Jan 4

Immune Regulation News 5.00 January 4, 2013
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Absence of Signaling into CD4+ Cells via C3aR and C5aR Enables Autoinductive TGF-β1 Signaling and Induction of Foxp3+ Regulatory T Cells
Investigators found that when signals from G protein–coupled receptors for the complement fragments C3a and C5a (C3aR and C5aR) were not transduced into CD4+ cells, signaling via the kinases PI(3)Kγ, Akt and mTOR ceased, activation of the kinase PKA increased, autoinductive signaling by transforming growth factor-β1 (TGF-β1) initiated and CD4+ T cells became Foxp3+ induced regulatory T cells. [Nat Immunol] Abstract

Air-Liquid Interface Culture for Respiratory Research: Watch Q&A Video
PUBLICATIONS (Ranked by impact factor of the journal)

Generation of Rejuvenated Antigen-Specific T Cells by Reprogramming to Pluripotency and Redifferentiation
Researchers reprogrammed clonally expanded antigen-specific CD8+ T cells from an HIV-1-infected patient to pluripotency. The T cell-derived induced pluripotent stem cells were then redifferentiated into CD8+ T cells that had a high proliferative capacity and elongated telomeres. [Cell Stem Cell]
Abstract | Press ReleaseGraphical Abstract

The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses
Scientists identified protein kinase C α (PKCα) as a signaling intermediate specific to the T helper 17 (Th17) cell subset in the activation of TGFβ receptor I (TGFβRI). They showed that PKCα physically interacts and functionally cooperates with TGFβRI to promote robust SMAD2-3 activation. [Immunity] Full Article

PDK1 Regulation of mTOR and Hypoxia-Inducible Factor 1 Integrate Metabolism and Migration of CD8+ T Cells
Investigators demonstrated that mammalian target of rapamycin complex 1 (mTORC1) activity in CD8+ T cells is not dependent on phosphatidylinositol-3 kinase or Akt but is critical to sustain glucose uptake and glycolysis in CD8+ T cells. [J Exp Med] Abstract | Press Release

Natural Killer Cells Promote Immune Tolerance by Regulating Inflammatory TH17 Cells at the Human Maternal-Fetal Interface
The authors found that decidual natural killer (NK) cells promote immune tolerance and successful pregnancy by dampening inflammatory TH17 cells via IFN-γ secreted by the CD56brightCD27+ NK subset. [Proc Natl Acad Sci USA] Abstract

CTLA-4 Controls the Thymic Development of Both Conventional and Regulatory T Cells through Modulation of the TCR Repertoire
Scientists investigated the thymic development of T cells in the presence and absence of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in a T-cell receptor (TCR) transgenic mouse model specific for the myelin basic protein peptide Ac1-9. [Proc Natl Acad Sci USA] Abstract

Foxp3+ Helios+ Regulatory T Cells Are Expanded in Active Systemic Lupus Erythematosus
Researchers hypothesized that Foxp3+ Helios+ regulatory T cells (T reg) may be of particular relevance in mediating immune tolerance in chronic autoimmunity as they possess enhanced suppressive function, compared to Foxp3+ Helios Treg. [Ann Rheum Dis] Abstract

Varicella Zoster-Specific CD4+Foxp3+ T Cells Accumulate after Cutaneous Antigen Challenge in Humans
The authors investigated the relationship between varicella zoster virus (VZV)-specific memory CD4+ T cells and CD4+Foxp3+ regulatory T cells that accumulate after intradermal challenge with a VZV skin test antigen. [J Immunol] Abstract

Transforming Growth Factor-β, Macrophage Colony-Stimulating Factor and C-Reactive Protein Levels Correlate with CD14highCD16+ Monocyte Induction and Activation in Trauma Patients
Scientists observed that the subpopulation of monocytes expressing high levels of CD14 and CD16 was expanded in a majority of patients. These cells also expressed CD163 consistent with differentiation into alternatively activated macrophages with potential regulatory or wound-healing activity. They examined factors in trauma plasma that may contribute to the generation and activation of these cells. [PLoS One]
Full Article

TLR4 Inactivation Protects from Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
To clarify the role of Toll-like receptor 4 (TLR4), which is a major receptor for bacterial lipopolysaccharides, in the development of acute graft-versus-host disease (GvHD), the authors used a TLR4-knockout mouse GvHD model and analyzed the underlying immunological mechanisms. [Cell Mol Immunol] Abstract

Learn more about the new smartphone app for human blood cell frequencies

Therapeutic Opportunities for Manipulating TReg Cells in Autoimmunity and Cancer
The authors discuss insights into the generation of regulatory T (TReg) cells, their involvement in disease and the molecular basis of the dominant tolerance exerted by forkhead box P3-expressing TReg cells that could permit their safe and specific manipulation in humans. [Nat Rev Drug Discov] Abstract

Receptos Doses First Patient in Phase II Trial for RPC1063 in Ulcerative Colitis
Receptos, Inc., announced that its selective sphingosine‐1‐ phosphate 1 receptor modulator, RPC1063, has been administered to the first patient in a phase II study examining the clinical efficacy and safety of induction therapy in patients with moderately to severely active ulcerative colitis. [PR Newswire Association LLC]
Press Release

Gradalis, Inc. Closes $24 Million in Series B Financing to Advance Late-Stage Trials of FANG™ Personalized Cancer Vaccine

Gradalis, Inc. announced that is has closed a $24 million Series B round of financing. Gradalis will use the funding to advance its autologous vaccine platform, FANG™, through late-stage clinical trials and expand manufacturing capabilities to accommodate commercial launch of FANG. [PR Newswire Association LLC] Press Release

XBiotech Receives Fast Track Designation from FDA for True Human™ Monoclonal Antibody Therapy Targeting Inflammatory Cytokine IL-1a for Restenosis

XBiotech announced that the company has been granted Fast Track designation by the FDA for its therapeutic monoclonal antibody MABp1 as a treatment to reduce the need for re-intervention after superficial femoral artery revascularization. [XBiotech USA, Inc.] Press Release


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NEW REGEN 2013 – Clinical Trials & Reimbursement
March 19-21, 2013
Boston, United States

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


Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

MSc – Future Opportunities (STEMCELL Technologies, Inc.)

PhD – Future Opportunities (STEMCELL Technologies, Inc.)

Postdoctoral Position – Tumor Stem Cells (Cancer Institute of New Jersey)

Postdoctoral Fellowship – HIV Research  (Sandra Rotman Centre for Global Health)

Postdoctoral Position – Lupus and Immunology Research (University of Chicago)

Postdoctoral Position – Immune Regulation (Trinity College Dublin)

Postdoctoral Position – Immunobiology Using Advanced Fluorescence-Based Techniques (Karolinska Institute)

Associate Scientist – Clinical Immunology (Crucell Holland B.V.)

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

PhD Research Position – Regulation of Dendritic Cells and Their Progenitors in Infectious Diseases (University of Tübingen)

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