NDLI: Control of T cell fates and immune tolerance by p38 signaling in mucosal CD103+ dendritic cells.

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Control of T cell fates and immune tolerance by p38 signaling in mucosal CD103+ dendritic cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Yanyan Huang, Gonghua Chi, Hongbo
Description	Country affiliation: United States Author Affiliation: Huang G ( Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.)
Abstract	Dendritic cells (DCs) play a crucial role in launching protective adaptive immunity against pathogens while maintaining immune tolerance to self-Ags. However, how intracellular signaling pathways program DCs to mediate tolerogenic responses remains largely unexplored. In this study, we describe that p38 signaling in CD103(+) mesenteric lymph node DCs reciprocally regulates the differentiation of anti-inflammatory induced regulatory T cells and proinflammatory Th1 cells from naive precursors and promotes mucosal tolerance. Deficiency of p38 in CD103(+) DCs inhibited the generation of induced regulatory T cells while promoting Th1 cell development in a TGF-ß2-dependent manner. Consequently, loss of p38 in DCs prevented induction of oral tolerance in vivo. Moreover, p38 in CD103(+) DCs was required for optimal expression of retinaldehyde dehydrogenase, a key enzyme for retinoic acid synthesis, which in turn imprinted gut-homing receptors on responding T cells. Consistent with a crucial role of p38 to program the tolerogenic activity of CD103(+) DCs, such DC subset contained constitutive activity of p38 and abundant expression of TGF-ß2 and retinaldehyde dehydrogenase. Our studies identify a key mechanism of DC-mediated coupling of T cell differentiation and trafficking that orchestrates mucosal immune tolerance.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1300398
Journal	The Journal of Immunology
Issue Number	2
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-07-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd Dendritic Cells Immunology Immune Tolerance Integrin Alpha Chains Mitogen-activated Protein Kinase 14 Metabolism T-lymphocytes, Regulatory Adaptive Immunity Animals Cell Differentiation Isoenzymes Biosynthesis Lymph Nodes Lymphocyte Activation Mice Mice, Inbred C57bl Mice, Knockout Retinal Dehydrogenase Signal Transduction Th1 Cells Transforming Growth Factor Beta2 Tretinoin Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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