Immune Regulation News Volume 7.03 | Jan 30 2015

​IL-10 Engages Macrophages to Shift Th17 Cytokine Dependency and Pathogenicity during T-Cell-Mediated Colitis
Investigators demonstrate using lineage-specific deletions of ​IL-10Rα that ​IL-10 acts primarily through macrophages to limit colitis. Lineage-specific effects of ​IL-10 skew the cytokine dependency of Th17 cell development required for colitis pathogenesis. [Nat Commun] Abstract

Immune-Mediated Antitumor Effect by Type 2 Diabetes Drug, Metformin
Metformin, a prescribed drug for type 2 diabetes, has been reported to have anti-cancer effects; however, the underlying mechanism is poorly understood. Researchers now show that this mechanism may be immune-mediated. [Proc Natl Acad Sci USA] Abstract | Full Article

Cross-Differentiation from the CD8 Lineage to CD4 T Cells in the Gut-Associated Microenvironment with a Nonessential Role of Microbiota
The authors report cross-differentiation from the CD8 lineage to CD4 T cells, but not vice versa, predominantly in the large-intestine-associated microenvironment. It occurred in the absence or distal presence of cognate antigens. [Cell Rep] Full Article | Graphical Abstract

Annexin-A1 Restricts Th17 Cells and Attenuates the Severity of Autoimmune Disease
Investigators used a T-cell mediated mouse model of retinal autoimmune disease to unravel the role of annexin-A1 in the development of autoreactive T helper cell responses and pathology. [J Autoimmun] Abstract

Unique Roles of TLR9- and MyD88-Dependent and -Independent Pathways in Adaptive Immune Responses to AAV-Mediated Gene Transfer
Researchers investigated the functions of toll-like receptor (TLR)2, TLR9 and the downstream signaling adaptor MyD88 in antibody and CD8⁺ T-cell responses. [J Innate Immun] Abstract

Differential Control of CD4⁺ T-Cell Subsets by the PD-1/PD-L1 Axis in a Mouse Model of Allergic Asthma
Using a mouse model of allergic asthma, researchers demonstrate that blockade of PD-1/PD-L1 has distinct influences on different CD4⁺ T-cell subsets. PD-1/PD-L1 blockade enhances airway hyperreactivity, not by altering the magnitude of the underlying Th2-type immune response, but by allowing the development of a concomitant Th17-type immune response. [Eur J Immunol] Abstract

Thymocyte-Derived BDNF Influences T Cell Maturation at the DN3/DN4 Transition Stage
Scientists investigated the impact of brain-derived neurotrophic factor (BDNF) on T cells using BDNF knockout (ko) mice and conditional ko mice lacking BDNF specifically in this lymphoid subset. In both settings, they observed diminished T-cell cellularity in peripheral lymphoid organs and an increase in CD4⁺CD44⁺ memory T cells. [Eur J Immunol] Abstract

Murine Pancreatic Adenocarcinoma Reduces Ikaros Expression and Disrupts T Cell Homeostasis
Scientists investigated the role of Ikaros in regulating T cell immune balance in pancreatic cancer mouse models. They suggest that the pancreatic tumor microenvironment may cause proteasomal degradation of Ikaros. This loss of Ikaros expression may contribute to an imbalance in T cell percentages. [PLoS One] Full Article

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Modeling EBV Infection and Pathogenesis in New-Generation Humanized Mice
Recent findings on the recapitulation of human Epstein-Barr virus (EBV) infection and pathogenesis in mouse models, as well as their application to preclinical studies of experimental anti-EBV therapies, are described. [Exp Mol Med] Full Article

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Gynecologic Oncology Group (GOG) Phase II Study of Advaxis’s Lm-LLO Immunotherapy, ADXS-HPV, for the Treatment of Persistent or Recurrent Cervical Cancer Achieves Safety and Efficacy Criteria
Advaxis, Inc. announced an update related to the Phase II open-label clinical study of ADXS-HPV in patients with persistent or recurrent cervical cancer with documented disease progression being conducted by the GOG. [Advaxis, Inc.] Press Release

Sorrento Announces Completion of Enrollment in the Cynviloq™ Registrational TRIBECA™ Study
Sorrento Therapeutics, Inc. announced that the last patient has been randomized in the ongoing TRIBECA™ (trial establishing bioequivalence between Cynviloq™ and albumin-bound paclitaxel) registrational trial. [Sorrento Therapeutics, Inc.] Press Release

VG Life Sciences Announces Issuance of Patent Covering Treatment of Inflammatory Bowel Disease with CLIP-Inducing Agent
VG Life Sciences announced the U.S. Patent and Trademark Office has issued U.S. Patent No. 8906846, covering a method of treating inflammatory bowel disease through the administration of a CLIP (class II-associated invariant chain peptide)-inducing agent. [VG Life Sciences Inc.] Press Release

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Postdoctoral Position – Immunology Animal Models (The Technical University of Denmark)

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Director (California Institute for Regenerative Medicine)

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Postdoctoral Position – HIV and Ebolavirus (University of Missouri)

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Postdoctoral Position – Immunology (Blood Research Institute, Blood Center of Wisconsin)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

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