Immune Regulation News Volume 9.43 | Nov 10 2017

TOP STORY

Immune Cells Mistake Heart Attacks for Viral Infections

A study led by Kevin King, a bioengineer and physician at the University of California, San Diego, has found that the immune system plays a surprising role in the aftermath of heart attacks. The research could lead to new therapeutic strategies for heart disease. [Press release from the University of California, San Diego discussing online prepublication in Nature Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

CD4⁺ T Cell Help Confers a Cytotoxic T Cell Effector Program including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness

Researchers present the transcriptomic changes in cytotoxic T cells (CTLs) resulting from CD4⁺ T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4⁺ T cell help during priming optimized CTLs in expression of cytotoxic effector molecules and many other functions that ensured efficacy of CTLs throughout their life cycle. [Immunity] Abstract | Graphical Abstract

The Cytokine TGF-β Promotes the Development and Homeostasis of Alveolar Macrophages

The authors report that alveolar macrophages (AMs), in contrast to most other tissue macrophages, were dependent on transforming growth factor-β receptor (TGF-βR) signaling. Conditional deletion of TGF-βR in mice at different time points halted the development and differentiation of AMs. [Immunity] Abstract | Graphical Abstract

CD38-NAD⁺Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response

Scientists established ex vivo culture conditions to generate hybrid Th1/17 cells, which persisted long-term in vivo while maintaining their effector function. Using transcriptomics and metabolic profiling approaches, they showed that the enhanced anti-tumor property of Th1/17 cells was dependent on the increased NAD⁺-dependent activity of the histone deacetylase Sirt1. [Cell Metab] Abstract | Press Release | Graphical Abstract

Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs

Using an autoimmune arthritis model, investigators showed that a constituent of the gut microbiota, segmented filamentous bacteria (SFB), distantly provoke lung pathology. SFB induced autoantibodies in lung during the pre-arthritic phase, and SFB-dependent lung pathology requires the T helper 17 (Th17) responses. [Cell Host Microbe] Abstract | Graphical Abstract

TRIM21 Negatively Regulates Intestinal Mucosal Inflammation through Inhibiting Th1/Th17 Cell Differentiation in Inflammatory Bowel Diseases

Researchers elucidated expression of tripartite motif-containing (TRIM)21 in patients with inflammatory bowel disease and its role in regulating intestinal mucosal inflammation. TRIM21 played a protective role in mucosal inflammation through inhibiting T helper (Th)1 and Th17 cell differentiation. [J Allergy Clin Immunol] Abstract

Pre-Metastatic Cancer Exosomes Induce Immune Surveillance by Patrolling Monocytes at the Metastatic Niche

Investigators showed that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These “non-metastatic” exosomes stimulated an innate immune response through the expansion of Ly6C^low patrolling monocytes in the bone marrow, which then caused cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages. [Nat Commun] Full Article

Metabolic Control of Regulatory T Cell (Treg) Survival and Function by Lkb1

Scientists showed that the metabolic sensor LKB1 is critical to maintain cellular metabolism and energy homeostasis in Tregs. Treg-specific deletion of Lkb1 in mice caused loss of Treg number and function, leading to a fatal, early-onset autoimmune disorder. [Proc Natl Acad Sci USA] Full Article | Press Release

Blocking Immunosuppression by Human Tregs In Vivo with Antibodies Targeting Integrin αvβ8

The authors showed that αVβ8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against αV or β8 subunits block TGF-β1 activation in vitro. They also showed that αV and β8 interact with GARP/latent TGF-β1 complexes in human Tregs. [Proc Natl Acad Sci USA] Abstract

Complement Activation via a C3a Receptor Pathway Alters CD4⁺ T Lymphocytes and Mediates Lung Cancer Progression

Researchers report mechanistic insights into this association in multiple immunocompetent orthotopic models of lung cancer. After tumor engraftment, they observed systemic activation of the complement cascade as reflected by elevated levels of the key regulator C3a. [Cancer Res] Abstract

Capacity of tTreg Generation Is Not Impaired in the Atrophied Thymus

The authors mechanistically studied thymic regulatory T (tTreg) cell generation in the atrophied thymus by utilizing both postnatal thymic epithelial cell-defective and naturally aged mouse models. They found that the capacity of tTreg cell generation was not impaired compared to CD4⁺ thymic conventional T cells, suggesting thymic atrophy positively influences tTreg cell generation. [PLoS Biol] Full Article

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Sentinels of the Type 2 Immune Response

Scientists discuss advances in the understanding of the interacting cellular subsets that comprise both primary and secondary type 2 responses. The studies described portray an immune response that depends upon well-organized tissue structures, and suggest their modulation as a therapeutic strategy. [Trends Immunol] Abstract

Immune Checkpoint Inhibition: Prospects for Prevention and Therapy of Hepatocellular Carcinoma

The authors review the roles that immune cells and cytokines have in the development of the most common primary liver cancer, hepatocellular carcinoma. [Clin Transl Immunology] Full Article

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Nektar Therapeutics Presents Preclinical Data on NKTR-358, a First-in-Class Regulatory T Cell Stimulator

Nektar Therapeutics presented preclinical data on NKTR-358, a potential first-in-class resolution therapeutic that may address the underlying immune system imbalance in patients with many immune conditions. [Press release from Nektar Therapeutics discussing research presented at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting, San Diego] Press Release

Ignyta Announces New Data Highlighting Immune Modulation of RXDX-106

Ignyta, Inc. announced new preclinical data for RXDX-106 – a novel immunomodulatory agent that demonstrated potent anti-tumor activity, alone and in combination with checkpoint inhibitors, by modulating the tumor microenvironment through TYRO3, AXL, and MER receptor tyrosine kinase inhibition. [Press release from Ignyta, Inc. discussing research presented at the 32^nd Annual Society for Immunotherapy of Cancer (SITC) Meeting, National Harbor] Press Release

Seattle Genetics and Astellas Initiate Phase Ib Trial of Enfortumab Vedotin in Combination with Immune Checkpoint Inhibitor Therapies in Locally Advanced or Metastatic Urothelial Cancer

Seattle Genetics, Inc. and Astellas Pharma Inc. announced dosing of the first patient in EV-103, a Phase Ib clinical trial evaluating the safety and tolerability of enfortumab vedotin in combination with pembrolizumab or atezolizumab, two types of immune checkpoint inhibitor therapies, for first- or second-line treatment of patients with locally advanced or metastatic urothelial cancer. [Seattle Genetics, Inc.] Press Release

BioLife Solutions and SAVSU Providing Enhanced Cold Chain Technologies for 8 UCSF Clinical Trials of Treg Cell Therapies

BioLife Solutions, Inc. and SAVSU announced both companies are providing their respective enhanced cold chain technologies for use in eight active and pending clinical trials conducted by the Diabetes Center and Department of Surgery at the University of California, San Francisco. [BioLife Solutions, Inc.] Press Release

US Government Approves ‘Killer’ Mosquitoes to Fight Disease

The US Environmental Protection Agency has approved the use of a common bacterium to kill wild mosquitoes that transmit viruses such as dengue, yellow fever and Zika. The agency told biotechnology start-up MosquitoMate that it could release the bacterium Wolbachia pipientis into the environment as a tool against the Asian tiger mosquito. [Nature News] Editorial

WHO Calls for Restrictions on Use of Antibiotics in Food Animal Production

The World Health Organization is urging countries to restrict the amount of antibiotics given in food animal production by prohibiting their routine use in growth promotion and disease prevention. The recommendation is one of a number the WHO issued aimed at preserving the effectiveness of antibiotics. [STAT News] Editorial

Court Demands that Search Engines and Internet Service Providers Block Sci-Hub

The American Chemical Society (ACS) has won a lawsuit against Sci-Hub, a website providing illicit free access to millions of paywalled scientific papers. ACS had alleged copyright infringement, trademark counterfeiting and trademark infringement; a district court in Virginia ruled that Sci-Hub should pay the ACS $4.8 million in damages after Sci-Hub representatives failed to attend court. [ScienceInsider] Editorial

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