Document Detail


Signaling via the kinase p38α programs dendritic cells to drive T(H)17 differentiation and autoimmune inflammation.
MedLine Citation:
PMID:  22231518     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 p38α programmed DCs to drive the differentiation of the T(H)17 subset of helper T cells. Deletion of p38α in DCs protected mice from T(H)17 cell-mediated autoimmune neuroinflammation, but deletion of p38α in macrophages or T cells did not. We also found that p38α 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, p38α was required for tissue-infiltrating DCs to sustain T(H)17 responses. This activity of p38α was conserved in mouse and human DCs and was dynamically regulated by pattern recognition and fungal infection. Our results identify p38α signaling as a central pathway for the integration of instructive signals in DCs for T(H)17 differentiation and inflammation.
Authors:
Gonghua Huang; Yanyan Wang; Peter Vogel; Thirumala-Devi Kanneganti; Kinya Otsu; Hongbo Chi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-08
Journal Detail:
Title:  Nature immunology     Volume:  -     ISSN:  1529-2916     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
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