PMID- 23752611
OWN - NLM
STAT- MEDLINE
DCOM- 20130918
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 191
IP  - 2
DP  - 2013 Jul 15
TI  - Control of T cell fates and immune tolerance by p38alpha signaling in mucosal CD103+ 
      dendritic cells.
PG  - 650-9
LID - 10.4049/jimmunol.1300398 [doi]
AB  - 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 p38alpha 
      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 p38alpha in CD103(+) DCs inhibited the generation of induced regulatory 
      T cells while promoting Th1 cell development in a TGF-beta2-dependent manner. 
      Consequently, loss of p38alpha in DCs prevented induction of oral tolerance in vivo. 
      Moreover, p38alpha 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 p38alpha to program the tolerogenic activity of CD103(+) DCs, such DC 
      subset contained constitutive activity of p38alpha and abundant expression of TGF-beta2 
      and retinaldehyde dehydrogenase. Our studies identify a key mechanism of 
      DC-mediated coupling of T cell differentiation and trafficking that orchestrates 
      mucosal immune tolerance.
FAU - Huang, Gonghua
AU  - Huang G
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 
      38105, USA.
FAU - Wang, Yanyan
AU  - Wang Y
FAU - Chi, Hongbo
AU  - Chi H
LA  - eng
GR  - R01 AI101407/AI/NIAID NIH HHS/United States
GR  - R01 NS064599/NS/NINDS NIH HHS/United States
GR  - R21 AI094089/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 - 20130610
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, CD)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Isoenzymes)
RN  - 0 (Transforming Growth Factor beta2)
RN  - 0 (alpha E integrins)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 1.2.1 (Aldehyde Dehydrogenase 1 Family)
RN  - EC 1.2.1.36 (ALDH1A1 protein, mouse)
RN  - EC 1.2.1.36 (Retinal Dehydrogenase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
SB  - IM
MH  - Adaptive Immunity
MH  - Aldehyde Dehydrogenase 1 Family
MH  - Animals
MH  - Antigens, CD/*analysis
MH  - Cell Differentiation
MH  - Dendritic Cells/*immunology/metabolism
MH  - *Immune Tolerance
MH  - Integrin alpha Chains/*analysis
MH  - Isoenzymes/biosynthesis
MH  - Lymph Nodes/immunology
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinase 14/*metabolism
MH  - Retinal Dehydrogenase/biosynthesis
MH  - Signal Transduction
MH  - T-Lymphocytes, Regulatory/*immunology
MH  - Th1 Cells/immunology
MH  - Transforming Growth Factor beta2/metabolism
MH  - Tretinoin/metabolism
PMC - PMC3702677
MID - NIHMS483329
EDAT- 2013/06/12 06:00
MHDA- 2013/09/21 06:00
PMCR- 2014/07/15
CRDT- 2013/06/12 06:00
PHST- 2013/06/12 06:00 [entrez]
PHST- 2013/06/12 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
PHST- 2014/07/15 00:00 [pmc-release]
AID - jimmunol.1300398 [pii]
AID - 10.4049/jimmunol.1300398 [doi]
PST - ppublish
SO  - J Immunol. 2013 Jul 15;191(2):650-9. doi: 10.4049/jimmunol.1300398. Epub 2013 Jun 
      10.