Immune Regulation News Volume 9.41 | Oct 27 2017

TOP STORY

IL-1R8 Is a Checkpoint in NK Cells Regulating Anti-Tumor and Anti-Viral Activity

Scientists report that IL-1R8 serves as a checkpoint for natural killer (NK) cell maturation and effector function. Its genetic blockade unleashed NK-cell-mediated resistance to hepatic carcinogenesis, hematogenous liver and lung metastasis, and cytomegalovirus infection. [Nature] Abstract

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Regulation of T Cell Alloimmunity by PI3Kγ and PI3Kδ

Investigators showed that both PI3Kγ^−/− and PI3Kδ^D910A/D910A mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection. However, PI3Kδ mutation also dampened Tregs. [Nat Commun] Full Article

DNA-Binding of the Tet-Transactivator Curtails Antigen-Induced Lymphocyte Activation in Mice

The authors showed that expression of the tetracycline/doxycycline-controlled Tet-transactivator, while tolerated well during development and in immunologically unchallenged animals, impairs the expansion of antigen-stimulated T and B cells and thereby curtails adaptive immune responses in vivo. [Nat Commun] Full Article

TCR-Stimulated Changes in Cell Surface CD46 Expression Generate Type 1 Regulatory T Cells

Scientists found that stimulation of the T cell receptor (TCR)–CD3 complex was associated with a reduction in the apparent molecular mass of CD46 in a manner that depended on O-glycosylation. CD3-stimulated changes in CD46 O-glycosylation status reduced CD46 processing and subsequent T cell signaling. [Sci Signal] Full Article

MyD88-Dependent Dendritic and Epithelial Cell Crosstalk Orchestrates Immune Responses to Allergens

By combining ATAC-seq with RNA profiling, researchers found that MyD88 signaling in conventional dendritic cells (cDCs) maintained open chromatin at select loci even at steady state, allowing genes to be rapidly induced during allergic sensitization. A distinct set of genes related to metabolism was indirectly controlled in cDCs through MyD88 signaling in airway epithelial cells. [Mucosal Immunol] Abstract

Sox2 Communicates with Tregs through CCL1 to Promote the Stemness Property of Breast Cancer Cells

Scientists disclose that the primarily cultured Tregs isolated from breast-tumor-bearing Foxp3–EGFP mouse up-regulate the stemness property of breast cancer cells. Tregs increased the side-population and the ALDH^br population of mouse breast cancer cells, promoted their sphere formation in a paracrine manner and enhanced the expression of stemness genes, such as Sox2 etc. [Stem Cells] Abstract

STAT4 Regulates the CD8⁺ Regulatory T Cell/T Follicular Helper Cell Axis and Promotes Atherogenesis in Insulin-Resistant Ldlr^−/− Mice

The authors generated Stat4^−/−Ldlr^−/− mice that were fed a diabetogenic diet with added cholesterol. They detected a reduction in T follicular helper cells and plasma B cells but a sharp elevation in CD8⁺ Tregs in spleens and aortas of Stat4^−/−Ldlr^−/− mice compared with Ldlr^−/− mice. [J Immunol] Abstract

RNA Editing by ADAR1 Regulates Innate and Antiviral Immune Functions in Primary Macrophages

Scientists determined the role of ADAR1 as a regulator of innate immune activation and modifier of viral susceptibility in primary myeloid and lymphoid cells. They showed that ADAR1 knockdown significantly enhanced interferon, cytokine and chemokine production in primary macrophages that function as antiviral paracrine factors, rendering them resistant to HIV-1 infection. [Sci Rep] Full Article

TC-PTP Regulates the IL-7 Transcriptional Response during Murine Early T Cell Development

Researchers identified T cell protein tyrosine phosphatase (TC-PTP), also known as PTPN2, as a negative regulator of IL-7R-STAT signaling in T cell progenitors, contributing to both the quantitative and qualitative nature of STAT-gene targeting. [Sci Rep] Full Article

Urban Particulate Matter Stimulation of Human Dendritic Cells Enhances Priming of Naïve CD8 T Lymphocytes

The authors examined the effects of urban particulate matter (UPM) on dendritic cell (DC)-stimulated naïve CD8 T cell responses. Treatment of myeloid DCs with UPM increased expression of CD83 and CCR7, but not MHC class I. [Immunology] Abstract

Analysis of the Regulatory Function of NK Cells from Patients with Systemic Lupus Erythematosus

Investigators evaluated the regulatory function of NK cells in systemic lupus erythematosus (SLE) patients and identified the NK cells involved in the pathogenesis of this complex disease. They found that SLE patients showed increased numbers of ILT2⁺, CD86⁺ and CD134+ NK cells. Furthermore, NK cells from SLE patients induced higher levels of DC lysis. [Clin Exp Immunol] Abstract

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Molecular Control of Regulatory T Cell Development and Function

Recent genome-wide studies have revealed that Foxp3⁺ natural Treg cells possess a number of unique transcriptional and epigenetic features, which appear to be acquired along the course of Treg cell development and maintained throughout their lifespan. [Curr Opin Immunol] Abstract

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Institut Curie and Pierre Fabre Initiate a Novel Partnership in Immuno-Oncology

Institut Curie and the Institut de Recherche Pierre Fabre will collaborate on new therapeutic strategies to advance cancer treatment for patients. The objective of this novel partnership is to dissect the biology of novel therapeutically tractable targets and evaluate the impact of innovative pharmacological approaches leveraging the Institut Curie’s biological models. [Institut de Recherche Pierre Fabre] Press Release

Dogs Offer New Hope for Lymphoma Research

Cornell and Tufts University scientists have received a five-year, $2.5 million grant from the National Institutes of Health to use dogs as a model for studying cancer immunotherapies. The grant also will more generally highlight the use of pet dogs as a model for studying human medicine, as they get many of the same diseases humans do. [Cornell University] Press Release

US March for Science Group Faces Growing Pains

The US group that sparked the global March for Science movement is facing complaints about its management practices as it files for non-profit status and signals its intent to continue as “a movement to advance science and its role in public life”. [Nature News] Editorial

Key Legislator Tells Trump Officials to Back Off on Proposed Overhead Spending Cap for NIH

An influential legislator wants President Donald Trump’s administration and fellow Republicans to drop the notion of capping overhead costs on grants funded by the National Institutes of Health (NIH). And that lawmaker, Representative Tom Cole, used his clout as chairman of the appropriations subcommittee that funds NIH to administer a dose of what he hopes will be preventive medicine. [ScienceInsider] Editorial

China Announces Plans to Fast-Track Drug Approval

China is overhauling its drug-approval system to let companies bring their treatments to market quicker and more easily. The Communist Party of China and the State Council, two of the country’s most authoritative bodies, announced plans to reduce the backlog of medicines awaiting approval by the China Food and Drug Administration. [Nature News] Editorial

NEW Wellcome Genome Campus: Single Cell Biology
March 6-8, 2018
Hinxton, United Kingdom

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