Immune Regulation News Volume 8.45 | Dec 9 2016

TOP STORY

The Chemokine Receptor CX3CR1 Defines Three Antigen-Experienced CD8 T Cell Subsets with Distinct Roles in Immune Surveillance and Homeostasis

Scientists found that the chemokine receptor CX3CR1 identifies three distinct CD8⁺ T effector (T_Eff) and T memory subsets. Classical central and effector memory cells and their corresponding T_Eff precursors were CX3CR1^– and CX3CR1^high, respectively. [Immunity] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

A Hypoxia-Responsive TRAF6–ATM–H2AX Signaling Axis Promotes HIF1α Activation, Tumorigenesis and Metastasis

Investigators showed that mono-ubiquitylation and phosphorylation of H2AX, which are strictly mediated by hypoxia-induced E3 ligase activity of TRAF6 and ATM, critically regulate HIF1α-driven tumorigenesis. [Nat Cell Biol] Abstract

Temporally Programmed CD8α⁺ DC Activation Enhances Combination Cancer Immunotherapy

In established syngeneic mouse tumor models, researchers found that staggering interferon-α administration after, rather than before or simultaneously with, serum-persistent interleukin-2 and tumor-specific antibody significantly increased long-term survival. [Cell Rep] Full Article | Graphical Abstract

Critical Role of TSLP-Responsive Mucosal Dendritic Cells in the Induction of Nasal Antigen-Specific IgA Response

Scientists found that the levels of thymic stromal lymphopoietin (TSLP) and TSLPR were upregulated in the mucosal dendritic cells of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin compared with those immunized with PspA alone. [Mucosal Immunol] Abstract

1-Methyl-Tryptophan Attenuates Regulatory T Cells Differentiation Due To the Inhibition of Estrogen-IDO1-MRC2 Axis in Endometriosis

The authors showed that the proportion of peritoneal regulatory T cells increases as endometriosis progresses. To determine the probable mechanism, they established a naive T cell-macrophage-endometrial stromal cell co-culture system to mimic the peritoneal cavity microenvironment. [Cell Death Dis] Full Article

Systemic Application of 3-Methyladenine Markedly Inhibited Atherosclerotic Lesion in ApoE^−/− Mice by Modulating Autophagy, Foam Cell Formation and Immune-Negative Molecules

Investigators tested the effect of two inhibitors of phosphatidylinositol 3-kinase, 3-methyladenine (3-MA) and 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), commonly used as inhibitors of autophagy, in atherosclerosis in apolipoprotein E^−/− mice. Systemic application of 3-MA but not LY294002 markedly reduced the size of atherosclerotic plaque and increased the stability of lesions in high-fat diet-fed mice as compared with controls. [Cell Death Dis] Full Article

Independent Control of Natural Killer Cell Responsiveness and Homeostasis at Steady-State by CD11c⁺ Dendritic Cells

The authors demonstrated that as early as 1 day after dendritic cell depletion, natural killer (NK) cells in naïve mice downregulated the NKG2D receptor and showed decreased constitutive phosphorylation of AKT and mTOR. Subsequently, apoptotic NK cells appeared in the spleen concomitant with reduced NK cell numbers. [Sci Rep] Full Article

Dynamics of Antigen Presentation to Transgene Product-Specific CD4⁺ T Cells and of Treg Induction upon Hepatic AAV Gene Transfer

Researchers administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells. They found that that the liver-draining lymph nodes are the major sites of MHC II presentation of the virally encoded antigen, as judged by in vivo proliferation of DO11.10 CD4⁺ T cells and CD4⁺CD25⁺FoxP3⁺ Treg induction. [Mol Ther Methods Clin Dev] Full Article

Cross-Talk between iNKT Cells and Monocytes Triggers an Atheroprotective Immune Response in SLE Patients with Asymptomatic Plaque

Accelerated atherosclerosis is a complication of the autoimmune rheumatic disease systemic lupus erythematosus (SLE). The authors questioned the role played by invariant natural killer T (iNKT) cells in this process because they not only are defective in autoimmunity but also promote atherosclerosis in response to CD1d-mediated lipid antigen presentation. [Sci Immunol] Abstract

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Immunoregulation by Members of the TGFβ Superfamily

The authors briefly outline the signaling pathways of the transforming growth factor-β (TGFβ) superfamily and discuss new insights into the immunoregulatory functions of bone morphogenetic proteins and activins in the context of infection, inflammation and cancer. [Nat Rev Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Late-Breaking Ibrutinib (IMBRUVICA^®) Data Show Complete or Partial Response in Two-Thirds of Patients with Chronic Graft-versus-Host-Disease, a Frequent and Potentially Life-Threatening Complication of Stem Cell Transplant

AbbVie announced positive results from a Phase II study evaluating ibrutinib in patients with chronic graft-versus-host-disease, a serious and debilitating potential consequence of stem cell or bone marrow transplant, who failed prior systemic therapy. [Press release from AbbVie Inc. discussing research presented at the 58^th American Society of Hematology (ASH) Annual Meeting and Exposition, San Diego] Press Release

BioLineRx Presents Positive Phase IIa AML Study and Mechanism-of-Action Data for BL-8040 Oncology Platform

BioLineRx Ltd. presented positive Phase IIa correlative data, as well as detailed mechanism-of-action data, for BL-8040, the company’s leading oncology platform. [Press release from BioLineRx Ltd. discussing research presented at the 58^th American Society of Hematology (ASH) Annual Meeting and Exposition, San Diego] Press Release

TxCell Signs In-Licensing Global Agreement with Inserm Transfert for Novel Population of Regulatory T Cells

TxCell SA and Inserm Transfert, on behalf of Inserm, the Nantes University and the Nantes CHU, announced the signature of an exclusive worldwide licensing agreement. [TxCell SA] Press Release

OncoQuest Initiates Commercial Scale Oregovomab Manufacturing Program for Treatment of Ovarian Cancer

OncoQuest Inc. announced that it has entered into an Antibody Manufacturing Development Program with Cytovance Biologics for its oregovomab antibody product. [OncoQuest Inc.] Press Release

Senate Sends Massive Biomedical Innovation Bill to Obama for Signing

By a 94-to-five vote, the Senate approved the 21^st Century Cures Act, clearing the way for President Barack Obama to sign the measure into law. The massive bill dedicates $4.8 billion over the next decade to research initiatives at the National Institutes of Health and makes an array of changes at the Food and Drug Administration designed to speed the approval of new drugs and medical devices. [ScienceInsider] Editorial

Controversial Impact Factor Gets a Heavyweight Rival

One of science’s most contentious metrics has a flashy new rival. Publishing giant Elsevier launched the CiteScore index to assess the quality of academic journals. Although the index ranks journals with a formula that largely mimics the influential Journal Impact Factor (JIF), it covers twice as many journals and its formula includes tweaks that produce some notably different results, including lower scores for some high-JIF journals. [Nature News] Editorial

NEW Keystone Symposium: Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology
March 19-23, 2017
Whistler, Canada

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

NEW Postdoctoral Position – Pre-Clinical In Vivo Studies and Immunology (German Cancer Research Center)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Precision Immunology (Icahn School of Medicine at Mount Sinai)

Postdoctoral Research Fellow – Cell Death and Immunity (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Immune Regeneration (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Immunology of HIV-1 and Cancer (University of Alabama at Birmingham)

Postdoctoral Researcher – Immunology/Molecular Biology (Duke University Department of Medicine)

Postdoctoral Position – Visceral Pain and Neuro-Immune Interaction (KU Leuven)

MRC WIMM Prize PhD Studentships – Various Projects (University of Oxford)

Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Molecular Immunology (University of California, San Diego)

Postdoctoral Fellow Position – Stem Cell Biology & Immunology (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

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