PMID- 22231518
OWN - NLM
STAT- MEDLINE
DCOM- 20120308
LR  - 20211021
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 13
IP  - 2
DP  - 2012 Jan 8
TI  - Signaling via the kinase p38alpha programs dendritic cells to drive TH17 
      differentiation and autoimmune inflammation.
PG  - 152-61
LID - 10.1038/ni.2207 [doi]
AB  - Dendritic cells (DCs) bridge innate and adaptive immunity, but how DC-derived 
      signals regulate T cell lineage choices remains unclear. We report here that the 
      mitogen-activated protein kinase p38alpha programmed DCs to drive the differentiation 
      of the T(H)17 subset of helper T cells. Deletion of p38alpha in DCs protected mice 
      from T(H)17 cell-mediated autoimmune neuroinflammation, but deletion of p38alpha in 
      macrophages or T cells did not. We also found that p38alpha orchestrated the 
      expression of cytokines and costimulatory molecules in DCs and further 
      'imprinted' signaling via the receptor for interleukin 23 (IL-23R) in responding 
      T cells to promote T(H)17 differentiation. Moreover, p38alpha was required for 
      tissue-infiltrating DCs to sustain T(H)17 responses. This activity of p38alpha was 
      conserved in mouse and human DCs and was dynamically regulated by pattern 
      recognition and fungal infection. Our results identify p38alpha signaling as a 
      central pathway for the integration of instructive signals in DCs for T(H)17 
      differentiation and inflammation.
FAU - Huang, Gonghua
AU  - Huang G
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, 
      Tennessee, USA.
FAU - Wang, Yanyan
AU  - Wang Y
FAU - Vogel, Peter
AU  - Vogel P
FAU - Kanneganti, Thirumala-Devi
AU  - Kanneganti TD
FAU - Otsu, Kinya
AU  - Otsu K
FAU - Chi, Hongbo
AU  - Chi H
LA  - eng
GR  - K01 AR053573-05/AR/NIAMS NIH HHS/United States
GR  - R01 NS064599-04/NS/NINDS NIH HHS/United States
GR  - K01 AR053573/AR/NIAMS NIH HHS/United States
GR  - R01 NS064599/NS/NINDS NIH HHS/United States
GR  - K01 AR053573-03S1/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120108
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Pattern Recognition)
RN  - 0 (interleukin-23 receptor, mouse)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
SB  - IM
MH  - Animals
MH  - Cytokines/immunology
MH  - Dendritic Cells/enzymology/*immunology
MH  - Encephalomyelitis, Autoimmune, Experimental/enzymology/*immunology
MH  - Gene Deletion
MH  - Humans
MH  - Lymphocyte Activation/*immunology
MH  - Macrophages/enzymology/immunology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 14/genetics/*metabolism
MH  - Mycoses/immunology/metabolism
MH  - Receptors, Interleukin/immunology
MH  - Receptors, Pattern Recognition/immunology/metabolism
MH  - T-Lymphocytes/enzymology/immunology
MH  - Th17 Cells/enzymology/*immunology
PMC - PMC3262925
MID - NIHMS342899
EDAT- 2012/01/11 06:00
MHDA- 2012/03/09 06:00
PMCR- 2012/08/01
CRDT- 2012/01/11 06:00
PHST- 2011/08/30 00:00 [received]
PHST- 2011/12/07 00:00 [accepted]
PHST- 2012/01/11 06:00 [entrez]
PHST- 2012/01/11 06:00 [pubmed]
PHST- 2012/03/09 06:00 [medline]
PHST- 2012/08/01 00:00 [pmc-release]
AID - ni.2207 [pii]
AID - 10.1038/ni.2207 [doi]
PST - epublish
SO  - Nat Immunol. 2012 Jan 8;13(2):152-61. doi: 10.1038/ni.2207.