IL-27 driven upregulation of surface HLA-e expression on monocytes inhibits IFN-γ release by autologous NK cells

Hla-g and hla-e are hla-ib molecules with several immunoregulatory properties. their cell surface expression can be modulated by different cytokines. since il-27 and il-30 may either stimulate or regulate immune responses,we have here tested whether these cytokines may modulate hla-g and -e expression and function on human monocytes. monocytes expressed gp130 and wsx-1,the two chains of il27 receptor (r),and il6r α (that serves as il-30r,in combination with gp130). however,only il27r appeared to be functional,as witnessed by il-27 driven stat1/ stat3 phosphorylation. il-27,but not il-30,significantly upregulated hla-e (but not hla-g) expression on monocytes. ifn- γ; secretion by activated nk cells was dampened when the latter cells were cocultured with il-27 pretreated autologous monocytes. such effect was not achieved using untreated or il-30 pretreated monocytes,thus indicating that il-27 driven hla-e upregulation might be involved,possibly through the interaction of this molecule with cd94/nkg2a inhibitory receptor on nk cells. in contrast,cytotoxic granules release by nk cell in response to k562 cells was unaffected in the presence of il-27 pretreated monocytes. in conclusion,we delineated a novel immunoregulatory function of il-27 involving hla-e upregulation on monocytes that might in turn indirectly impair some nk cell functions. © 2014 fabio morandi et al.