Soluble HLA-G dampens CD94/NKG2A expression and function and differentially modulates chemotaxis and cytokine and chemokine secretion in CD56bright and …

F Morandi, E Ferretti, R Castriconi… - Blood, The Journal …, 2011 - ashpublications.org
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
Abstract Soluble HLA-G (sHLA-G) inhibits natural killer (NK) cell functions. Here, we
investigated sHLA-G–mediated modulation of (1) chemokine receptor and NK receptor
expression and function and (2) cytokine and chemokine secretion in CD56bright and
CD56dim 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 down-modulated (1) CXCR3 on PB and tonsil CD56bright and CD56dim,(2) CCR2 on PB …
Abstract
Soluble HLA-G (sHLA-G) inhibits natural killer (NK) cell functions. Here, we investigated sHLA-G–mediated modulation of (1) chemokine receptor and NK receptor expression and function and (2) cytokine and chemokine secretion in CD56bright and CD56dim 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 down-modulated (1) CXCR3 on PB and tonsil CD56bright and CD56dim, (2) CCR2 on PB and tonsil CD56bright, (3) CX3CR1 on PB CD56dim, (4) CXCR5 on tonsil CD56dim, and (5) CD94/NKG2A on PB and tonsil CD56bright and CD56dim NK cells. Such sHLA-G–mediated down-modulations were reverted by adding anti–HLA-G or anti–ILT2 mAbs. sHLA-G inhibited chemotaxis of (1) PB NK cells toward CXCL10, CXCL11, and CX3CL1 and (2) PB CD56bright NK cells toward CCL2 and CXCL10. IFN-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 (1) CCL22 in CD56bright and CD56dim and (2) CCL2, CCL8, and CXCL2-CXCL3 in CD56dim PB NK cells. Signal transduction experiments showed sHLA-G–mediated down-modulation of Stat5 phosphorylation in PB NK cells. In conclusion, our data delineated novel mechanisms of sHLA-G–mediated inhibition of NK-cell functions.
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