FcαRI-Mediated Inhibition of IL-12 Production and Priming by IFN-γ of Human Monocytes and Dendritic Cells

We showed that IgA induces IL-10 in monocytes and dendritic cells. Because reciprocal inhibition exists between IL-10 and IL-12, we explored whether IgA could regulate this other immunoregulatory cytokine. In human monocytes and monocyte-derived dendritic cells preincubated with IFN-gamma before stimulation by LPS, suppression of p40 and IL-12p70 production was observed upon IgA treatment during IFN-gamma priming. Washout experiments and inhibition of IFN-gamma-induced CXCL10 (IP-10) and Fc gamma RI (CD64) indicated that inhibition by IgA occurred at both the LPS and IFN-gamma levels. Inhibition was not affected by blockade of IL-10 or MAPK but involved Fc alpha RI/CD89-mediated suppression of STAT1 phosphorylation. These data indicate that Fc alpha RI ligation on human monocytes and dendritic cells inhibits IL-12 expression and type 1 activation by interfering with STAT1 activation. The Journal of Immunology, 2013, 190: 2362-2371.