Volume 4.36 | Sep 21

Immune Regulation News 4.36 September 21, 2012
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BATF-JUN Is Critical for IRF4-Mediated Transcription in T Cells
The authors showed that activator protein-1 (AP1) and interferon regulatory factor 4 (IRF4) complexes cooperatively promote transcription of the Il10 gene, which is expressed in TH17 cells and potently regulated by IL-21. These findings reveal that IRF4 can signal via complexes containing ETS or AP1 motifs depending on the cellular context, thus indicating new approaches for modulating IRF4-dependent transcription. [Nature] Abstract

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The Cytokines Interleukin 27 and Interferon-γ Promote Distinct Treg Cell Populations Required to Limit Infection-Induced Pathology
Researchers found that interferon-γ and interleukin-27 (IL-27) have different roles in regulatory T (Treg) cell biology and IL-27 is a key cytokine that promotes the development of Treg cells specialized to control T helper 1 cell-mediated immunity at local sites of inflammation. [Immunity] Abstract

Tet2 Facilitates the Derepression of Myeloid Target Genes during CEBPα-Induced Transdifferentiation of Pre-B Cells
Researchers’ observations indicated that Tet2 helps CEBPα rapidly derepress myeloid genes during the conversion of pre-B cells into macrophages. [Mol Cell] Abstract

Outer Membrane Vesicles of a Human Commensal Mediate Immune Regulation and Disease Protection
Investigators revealed that Bacteroides fragilis releases polysaccharide (PSA) in outer membrane vesicles (OMVs) that induce immunomodulatory effects and prevent experimental colitis. Dendritic cells sense OMV-associated PSA through TLR2, resulting in enhanced regulatory T cells and anti-inflammatory cytokine production. [Cell Host Microbe] Abstract

Mutant Huntingtin Fragmentation in Immune Cells Tracks Huntington’s Disease Progression
Peripheral immune cells have been implicated in Huntington’s disease (HD) pathogenesis, but huntingtin (HTT) levels in these cells have not been quantified before. A recently described time-resolved Förster resonance energy transfer immunoassay was used to quantify mutant and total HTT protein levels in leukocytes from patients with HD. [J Clin Invest] Full Article | Press Release

TAp73 Is Required for Macrophage-Mediated Innate Immunity and the Resolution of Inflammatory Responses
Scientists investigated whether TAp73 contributes to innate immunity and septic shock. Their data indicated that TAp73 has a role in macrophage polarization and innate immunity, enhancing the action field of this important regulatory molecule. [Cell Death Differ] Abstract

Cell-Intrinsic Abrogation of TGF-β Signaling Delays but Does Not Prevent Dysfunction of Self/Tumor-Specific CD8 T Cells in a Murine Model of Autochthonous Prostate Cancer
Researchers used a model of autochthonous murine prostate cancer to evaluate the effect of cell-intrinsic abrogation of TGF-β signaling in self/tumor-specific CD8 T cells used in adoptive T cell therapy to target the tumor in situ. [J Immunol] Abstract

B7x in the Periphery Abrogates Pancreas-Specific Damage Mediated by Self-Reactive CD8 T Cells
Results suggest that B7x in nonlymphoid organs prevents peripheral autoimmunity partially through inhibiting proliferation of tissue-specific CD8 T cells, and that local overexpression of B7x on pancreatic β cells is sufficient to abolish CD8 T cell-induced diabetes. [J Immunol] Abstract

Airway Epithelial Cells Condition Dendritic Cells to Express Multiple Immune Surveillance Genes
Findings suggest that airway epithelial cell conditioning facilitates the capacity of dendritic cells to react to danger signals, to enhance leukocyte recruitment, especially of Th1 effector cells, and to interact with other immune cell populations while minimizing the risks of excessive inflammation leading to tissue damage. [PLoS One] Full Article

Toll-Like Receptor 3 Activation Differentially Regulates Phagocytosis of Bacteria and Apoptotic Neutrophils by Mouse Peritoneal Macrophages
Researchers found that Toll-like receptor 3 activation promotes bacterial uptake through the activation of interferon-regulating factor 3 and inhibits phagocytosis of apoptotic neutrophils through the activation of nuclear factor-κB by mouse peritoneal macrophages. [Immunol Cell Biol] Abstract

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Metabolic Checkpoints in Activated T Cells
The availability of specific metabolites and the pathways that process them interconnect with signaling events in the cell to influence cell cycle, differentiation, cell death and immunological function. Researchers defined ‘metabolic checkpoints’ that represent such interconnections and provide examples of how these checkpoints sense metabolic status and transduce signals to affect T lymphocyte responses. [Nat Immunol] Abstract

T Cells Out of Control-Impaired Immune Regulation in the Inflamed Joint
This review summarizes the latest findings on changes in effector T cell homeostasis in autoimmune disease and focuses on how mechanisms that normally regulate these cells are affected in the inflamed joints of patients with arthritis. [Nat Rev Rheumatol] Abstract

Jennerex Presents Positive Clinical Data from Phase II Trial of JX594 in Sorafenib-Refractory Liver Cancer Patients
Jennerex, Inc. presented Phase II clinical data of JX594 delivered first intravenously and subsequently through intra-tumoral route demonstrating safety as well as disease control and tumor responses in patients with hepatocellular carcinoma. [Press release from Jennerex, Inc. discussing research presented at the International Liver Cancer Association (ILCA) Annual Meeting, Berlin] Press Release

NewLink Announces an Investigator Initiated Phase II Study of Sipuleucel-T Plus Indoximod in the Treatment of Certain Men with Advanced Prostate Cancer
NewLink Genetics announced that it will begin an investigator initiated, randomized, double blind placebo controlled Phase II study entitled “Phase II Study of sipuleucel-T (PROVENGE®) plus indoximod (D-1MT/NLG8189) in the treatment of patients with asymptomatic or minimally symptomatic metastatic hormone refractory prostate cancer.” [NewLink Genetics Corporation] Press Release

China to Cut Prices of Cancer, Immunology and Blood Drugs
China will cut the maximum retail prices of 95 cancer, immunology and blood-related drugs by about 17 percent to try to reduce the growing number of chronic, ageing-related diseases in the country and make healthcare more affordable. [Reuters] Press Release


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June 14-16, 2013
Suzhou, China

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