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The interleukin-36 receptor pathway regulates Aspergillus fumigatus-induced Th1 and Th17 responses.
MedLine Citation:
PMID:  23147407     Owner:  NLM     Status:  Publisher    
IL-1 drives T-helper responses, particularly Th17, in host defense. Sharing the same co-receptor, the IL-1 family member IL-36 exhibits properties similar to those of IL-1. In the present study, we investigated the role of IL-36 in Aspergillus fumigatus-induced human T-helper cell responses. We observed that different morphological forms of A. fumigatus variably increase steady-state mRNA of IL-36 subfamily members. IL-36α is not significantly induced by any morphological form of Aspergillus. Most strikingly, IL-36γ is significantly induced by live A. fumigatus conidia and heat killed hyphae, whereas IL-36Ra is significantly induced by heat killed conidia, hyphae and live conidia. We also observed that IL-36γ expression is dependent on the dectin-1/Syk and TLR4 signaling pathway. In contrast, TLR2 and CR3 inhibit IL-36γ expression. The biological relevance of IL-36 induction by Aspergillus is demonstrated by experiments showing that inhibition of the IL-36 receptor by IL-36Ra reduces Aspergillus-induced IL-17 and IFN-γ. These data describe that IL-36-dependent signals are a novel cytokine pathway that regulates T-helper responses induced by A. fumigatus, and demonstrate a role for TLR4 and dectin-1 in the induction of IL-36γ.
Mark S Gresnigt; Berenice Rösler; Cor W M Jacobs; Katharina L Becker; Leo A B Joosten; Jos W M van der Meer; Mihai G Netea; Charles A Dinarello; Frank L van de Veerdonk
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-12
Journal Detail:
Title:  European journal of immunology     Volume:  -     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Department of Medicine, Radboud University Nijmegen Medical Centre and Nijmegen Institute for Infection, Inflammation, and Immunity (N4i), Nijmegen, the Netherlands.
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