PMID- 26170384
OWN - NLM
STAT- MEDLINE
DCOM- 20151124
LR  - 20181113
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 195
IP  - 4
DP  - 2015 Aug 15
TI  - Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That 
      Require Hopx To Inhibit Intrinsic IL-2 Expression.
PG  - 1489-97
LID - 10.4049/jimmunol.1500174 [doi]
AB  - 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.
CI  - Copyright (c) 2015 by The American Association of Immunologists, Inc.
FAU - Jones, Andrew
AU  - Jones A
AD  - Department of Molecular Microbiology and Immunology, Saint Louis University 
      School of Medicine, St. Louis, MO 63104;
FAU - Opejin, Adeleye
AU  - Opejin A
AD  - Department of Molecular Microbiology and Immunology, Saint Louis University 
      School of Medicine, St. Louis, MO 63104;
FAU - Henderson, Jacob G
AU  - Henderson JG
AD  - Department of Molecular Microbiology and Immunology, Saint Louis University 
      School of Medicine, St. Louis, MO 63104;
FAU - Gross, Cindy
AU  - Gross C
AD  - Department of Molecular Microbiology and Immunology, Saint Louis University 
      School of Medicine, St. Louis, MO 63104;
FAU - Jain, Rajan
AU  - Jain R
AD  - Department of Cell and Developmental Biology and Institute for Regenerative 
      Medicine and Cardiovascular Institute, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104; and.
FAU - Epstein, Jonathan A
AU  - Epstein JA
AD  - Department of Cell and Developmental Biology and Institute for Regenerative 
      Medicine and Cardiovascular Institute, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104; and.
FAU - Flavell, Richard A
AU  - Flavell RA
AD  - Department of Immunobiology and Howard Hughes Medical Institute, Yale University 
      School of Medicine, New Haven, CT 06519.
FAU - Hawiger, Daniel
AU  - Hawiger D
AD  - Department of Molecular Microbiology and Immunology, Saint Louis University 
      School of Medicine, St. Louis, MO 63104; dhawiger@slu.edu.
LA  - eng
GR  - K08 HL119553/HL/NHLBI NIH HHS/United States
GR  - R01 AI113903/AI/NIAID NIH HHS/United States
GR  - R01 HL071546/HL/NHLBI NIH HHS/United States
GR  - R01AI113903/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150713
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Autoantigens)
RN  - 0 (Hod protein, mouse)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Interleukin-2)
SB  - IM
MH  - Animals
MH  - Autoantigens/immunology
MH  - Autoimmunity/genetics/immunology
MH  - Dendritic Cells/immunology/metabolism
MH  - Disease Models, Animal
MH  - *Gene Expression Regulation
MH  - Homeodomain Proteins/*genetics
MH  - Immune Tolerance/*genetics
MH  - Inflammation/genetics/immunology/metabolism
MH  - Interleukin-2/*genetics
MH  - Mice
MH  - Mice, Knockout
MH  - T-Lymphocytes, Regulatory/*immunology/*metabolism
PMC - PMC4530038
MID - NIHMS702145
EDAT- 2015/07/15 06:00
MHDA- 2015/12/15 06:00
PMCR- 2016/08/15
CRDT- 2015/07/15 06:00
PHST- 2015/01/26 00:00 [received]
PHST- 2015/06/15 00:00 [accepted]
PHST- 2015/07/15 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2016/08/15 00:00 [pmc-release]
AID - jimmunol.1500174 [pii]
AID - 10.4049/jimmunol.1500174 [doi]
PST - ppublish
SO  - J Immunol. 2015 Aug 15;195(4):1489-97. doi: 10.4049/jimmunol.1500174. Epub 2015 
      Jul 13.