Immune Regulation News Volume 7.15 | May 1 2015

T_H17 Cells Transdifferentiate into Regulatory T Cells during Resolution of Inflammation
Scientists used two new fate-mapping mouse models to track T helper 17 (T_H17) cells during immune responses to show that CD4⁺ T cells that formerly expressed IL-17A go on to acquire an anti-inflammatory phenotype. The transdifferentiation of TH17 into regulatory T cells was illustrated by a change in their signature transcriptional profile and the acquisition of potent regulatory capacity. [Nature] Abstract | Press Release

Group 3 Innate Lymphoid Cells Mediate Intestinal Selection of Commensal Bacteria-Specific CD4⁺ T Cells
Investigators demonstrate that group 3 innate lymphoid cell (ILC3)–intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII⁺ ILC3s directly induce cell death of activated commensal bacteria-specific T cells. [Science]
Abstract | Press Release

Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli
Mecp2 was found to be expressed in peripheral macrophage and monocyte populations, several of which also became depleted in Mecp2-null mice. RNA-seq revealed increased expression of glucocorticoid- and hypoxia-induced transcripts in Mecp2-deficient microglia and peritoneal macrophages. [Immunity]
Abstract | Graphical Abstract | Press Release

SIRT1 Deacetylates RORγT and Enhances Th17 Cell Generation
Scientists report that Sirtuin 1 (SIRT1), a protein deacetylase previously reported to have an antiinflammatory function, in fact promotes autoimmunity by deacetylating RORγt, the signature transcription factor of T helper 17 (Th17) cells. [J Exp Med] Abstract | Press Release

A Dominant Role for the Methyl-CpG-Binding Protein Mbd2 in Controlling Th2 Induction by Dendritic Cells
Investigators demonstrate a key role for the protein Mbd2, which links DNA methylation to repressive chromatin structure, in regulating expression of a range of genes that are associated with optimal dendritic cell activation and function. [Nat Commun] Full Article | Press Release

Association of CLEC16A with Human Common Variable Immunodeficiency Disorder and Role in Murine B Cells
Clec16a knockdown mice showed reduced number of B cells and elevated IgM levels compared with controls, suggesting that CLEC16A may be involved in immune regulatory pathways of relevance to common variable immunodeficiency disorder. [Nat Commun] Abstract | Press Release

Macrophages Are Critical to the Maintenance of IL-13-Dependent Lung Inflammation and Fibrosis
Using CD11b-diphtheria toxin receptor transgenic mice and three models of interleukin 13-dependent inflammation, fibrosis, and immunity, investigators showed that CD11b⁺ F4/80⁺ Ly6C⁺ macrophages are required for the maintenance of type 2 immunity within affected tissues but not secondary lymphoid organs. [Mucosal Immunol] Abstract

Innate and Adaptive Immune Functions of Peyer’s Patch Monocyte-Derived Cells
The authors show that monocytes give rise to macrophages and to lysozyme-expressing dendritic cells, which are both involved in particulate antigen uptake, display strong innate antiviral and antibacterial gene signatures, and, upon TLR7 stimulation, secrete IL-6 and TNF, but neither IL-10 nor IFNγ. [Cell Rep]
Full Article | Graphical Abstract

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Lycera Initiates Phase I Clinical Trial of LYC-30937, a First-In-Class ATPase Modulator for Inflammatory Bowel Disease
Lycera Corp. announced the initiation of a Phase I clinical trial of LYC-30937 in healthy volunteers. LYC-30937 is designed to selectively induce cell death in disease-causing immune cells, sparing normal cells. [Lycera Corp.] Press Release

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