Document Detail


Leishmania donovani-induced expression of signal regulatory protein alpha on Kupffer cells enhances hepatic invariant NKT-cell activation.
MedLine Citation:
PMID:  19877019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Signal regulatory protein alpha (SIRPalpha) and its cognate ligand CD47 have been documented to have a broad range of cellular functions in development and immunity. Here, we investigated the role of SIRPalpha-CD47 signalling in invariant NKT (iNKT) cell responses. We found that CD47 was required for the optimal production of IFN-gamma from splenic iNKT cells following exposure to the alphaGalCer analogue PBS-57 and in vivo infection of mice with Leishmania donovani. Surprisingly, although SIRPalpha was undetectable in the liver of uninfected mice, the hepatic iNKT-cell response to infection was also impaired in CD47-/- mice. However, we found that SIRPalpha was rapidly induced on Kupffer cells following L. donovani infection, via a mechanism involving G-protein-coupled receptors. Thus, we describe a novel amplification pathway affecting cytokine production by hepatic iNKT cells, which may facilitate the breakdown of hepatic tolerance after infection.
Authors:
Lynette Beattie; Mattias Svensson; Alison Bune; Najmeeyah Brown; Asher Maroof; Soombul Zubairi; Katharine R Smith; Paul M Kaye
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  40     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-04     Completed Date:  2010-01-19     Revised Date:  2010-09-28    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  117-23     Citation Subset:  IM    
Affiliation:
Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD47 / genetics,  immunology
Immune Tolerance
Kupffer Cells / immunology*
Leishmania donovani / immunology*
Leishmaniasis, Visceral / immunology*
Liver / immunology*
Lymphocyte Activation*
Mice
Mice, Knockout
Natural Killer T-Cells / immunology*
Receptors, Immunologic / immunology*
Grant Support
ID/Acronym/Agency:
//Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Antigens, CD47; 0/Ptpns1 protein, mouse; 0/Receptors, Immunologic
Comments/Corrections

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