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-γ before stimulation by LPS, suppression of p40 and IL-12p70 production was observed upon IgA treatment during IFN-γ priming. Washout experiments and inhibition of IFN-γ-induced CXCL10 (IP-10) and FcγRI (CD64) indicated that inhibition by IgA occurred at both the LPS and IFN-γ levels. Inhibition was not affected by blockade of IL-10 or MAPK but involved FcαRI/CD89-mediated suppression of STAT1 phosphorylation. These data indicate that FcαRI ligation on human monocytes and dendritic cells inhibits IL-12 expression and type 1 activation by interfering with STAT1 activation.
Institut de Recherche Expérimentale et Clinique, Pôle Pneumologie, ORL et Dermatologie, B-1200 Brussels, Belgium. charles.pilette@uclouvain.be
Marylène
M
Lecocq
Bruno
B
Detry
Amélie
A
Guisset
Charles
C
Pilette
D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D000072000:NF-KappaB Inhibitor alpha; D010766:Phosphorylation / Q000187:drug effects; D011961:Receptors, Fc / Q000235:genetics* / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
D015703:Antigens, CD; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C489017:FCGR1A protein, human; C036832:Fc(alpha) receptor; D020672:I-kappa B Proteins; C508609:IL10 protein, human; D007070:Immunoglobulin A; D008070:Lipopolysaccharides; C000606204:NFKBIA protein, human; D011961:Receptors, Fc; D017452:Receptors, IgG; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D016753:Interleukin-10; D000072000:NF-KappaB Inhibitor alpha; D018664:Interleukin-12; D007371:Interferon-gamma