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 CD56 bright and CD56 dim NK cells. sHLA-Gtreated 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 CD56 bright and CD56 dim, (2) CCR2 on PB and tonsil CD56 bright, (3) CX 3CR1 on PB CD56 dim, (4) CXCR5 on tonsil CD56 dim, and (5) CD94/NKG2A on PB and tonsil CD56 bright and CD56 dimNK cells. Such sHLA-G-mediated downmodulations were reverted by adding anti-HLA-G or anti-ILT2 mAbs. sHLA-G inhibited chemotaxis of (1) PB NK cells toward CXCL10, CXCL11, and CX 3CL1 and (2) PB CD56 bright 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 CD56 bright and CD56 dim and (2) CCL2, CCL8, and CXCL2-CXCL3 in CD56 dim 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.
ASJC Scopus subject areas
- Cell Biology