Document Detail


Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine/chemokine secretion in CD56bright and CD56dim NK cells.
MedLine Citation:
PMID:  21989990     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Soluble HLA-G (sHLA-G) inhibits NK cell functions. Here we investigated sHLA-G-mediated modulation of i) chemokine receptor and NK receptor expression and function and ii) cytokine/chemokine secretion in CD56(bright) and CD56(dim) NK cells. sHLA-G-treated or untreated peripheral blood (PB) and tonsil NK cells were analyzed for chemokine receptor and NK receptor expression by flow cytometry. sHLA-G downmodulated i) CXCR3 on PB and tonsil CD56(bright) and CD56(dim) , ii) CCR2 on PB and tonsil CD56(bright), iii) CX3CR1 on PB CD56(dim) , iv) CXCR5 on tonsil CD56(dim) and v) CD94/NKG2A on PB and tonsil CD56(bright) and CD56(dim) NK cells. Such sHLA-G-mediated downmodulations were reverted by adding anti-HLA-G or anti-ILT2 mAbs. sHLA-G inhibited chemotaxis of i) PB NK cells towards CXCL10, CXCL11 and CX3CL1 and ii) PB CD56(bright) NK cells towards CCL2 and CXCL10. Interferon-γ secretion induced by NKp46 engagement was inhibited by NKG2A engagement in untreated but not in sHLA-G-treated NK cells. sHLA-G up-regulated secretion of i) CCL22 in CD56(bright) and CD56(dim) and ii) CCL2, CCL8 and CXCL2-CXCL3 in CD56(dim) PB NK cells. Signal transduction experiments showed sHLA-G-mediated downmodulation of Stat5 phosphorylation in PB NK cells. In conclusion, our data delineated novel mechanisms of sHLA-G-mediated inhibition of NK cell functions.
Authors:
Fabio Morandi; Elisa Ferretti; Roberta Castriconi; Alessandra Dondero; Andrea Petretto; Cristina Bottino; Vito Pistoia
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-11
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Oncology, G.Gaslini Scientific Institute, Genoa, Italy;
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