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C5a receptor signalling in dendritic cells controls the development of maladaptive Th2 and Th17 immunity in experimental allergic asthma.
MedLine Citation:
PMID:  23212198     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The pathways underlying dendritic cell (DC) activation in allergic asthma are incompletely understood. Here we demonstrate that adoptive transfer of ovalbumin-pulsed wild-type (wt) but not of C5a receptor-deficient (C5aR(-/-)) bone marrow (BM)-derived DCs (BMDCs) induced mixed T helper type 2 (Th2)/Th17 maladaptive immunity, associated with severe airway hyperresponsiveness, mucus production, and mixed eosinophilic/neutrophilic inflammation. Mechanistically, antigen uptake, processing, and CD11b expression were reduced in C5aR(-/-) BMDCs. Further, interleukin (IL)-1β, -6, and -23 production were impaired resulting in reduced Th17 cell differentiation, associated with accelerated activated T-cell death in vitro and in vivo. Surprisingly, we found an increased frequency of CD11b(hi)CD11c(int)Gr1(+)F4/80(+) cells, expressing arginase and nitric oxide synthase in C5aR(-/-) BM preparations. Intratracheal administration of ovalbumin-pulsed wt DCs and sorted CD11b(hi)CD11c(int)Gr1(+)F4/80(+) C5aR(-/-) cells reduced Th2 immune responses in vivo. Together, we uncover novel roles for C5aR in Th17 differentiation, T-cell survival, and differentiation of a DC-suppressor population controlling Th2 immunity in experimental allergic asthma.Mucosal Immunology advance online publication 5 December 2012; doi:10.1038/mi.2012.119.
Authors:
I Schmudde; H A Ströver; T Vollbrandt; P König; C M Karsten; Y Laumonnier; J Köhl
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-05
Journal Detail:
Title:  Mucosal immunology     Volume:  -     ISSN:  1935-3456     ISO Abbreviation:  Mucosal Immunol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101299742     Medline TA:  Mucosal Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
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