NDLI: Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That Require Hopx To Inhibit Intrinsic IL-2 Expression.

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Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That Require Hopx To Inhibit Intrinsic IL-2 Expression.

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Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That Require Hopx To Inhibit Intrinsic IL-2 Expression.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Flavell, Richard A. Opejin, Adeleye Hawiger, Daniel Jain, Rajan Henderson, Jacob G. Gross, Cindy Jones, Andrew Epstein, Jonathan A.
Description	Author Affiliation: Jones A ( Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104); Opejin A ( Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104); Henderson JG ( Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104); Gross C ( Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104); Jain R ( Department of Cell and Developmental Biology and Institute for Regenerative Medicine and Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104); Epstein JA ( Department of Cell and Developmental Biology and Institute for Regenerative Medicine and Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104); Flavell RA ( Department of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06519.); Hawiger D ( Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104)
Abstract	Dendritic cells (DCs) can induce peripheral immune tolerance that prevents autoimmune responses. Ag presentation by peripheral DCs under steady-state conditions leads to a conversion of some peripheral CD4(+) T cells into regulatory T cells (Tregs) that require homeodomain-only protein (Hopx) to mediate T cell unresponsiveness. However, the roles of these peripheral Tregs (pTregs) in averting autoimmune responses, as well as immunological mechanisms of Hopx, remain unknown. We report that Hopx(+) pTregs converted by DCs from Hopx(-) T cells are indispensible to sustain tolerance that prevents autoimmune responses directed at self-Ags during experimental acute encephalomyelitis. Our studies further reveal that Hopx inhibits intrinsic IL-2 expression in pTregs after antigenic rechallenge. In the absence of Hopx, increased levels of IL-2 lead to death and decreased numbers of pTregs. Therefore, formation of Hopx(+) pTregs represents a crucial pathway of sustained tolerance induced by peripheral DCs, and the maintenance of such pTregs and tolerance requires functions of Hopx to block intrinsic IL-2 production in pTregs.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1500174
Journal	The Journal of Immunology
Issue Number	4
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gene Expression Regulation Homeodomain Proteins Genetics Immune Tolerance Interleukin-2 T-lymphocytes, Regulatory Immunology Metabolism Animals Autoantigens Autoimmunity Dendritic Cells Disease Models, Animal Inflammation Mice Mice, Knockout 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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