Inhibition of murine fibrocyte differentiation by cross-linked IgG is dependent on FcγRI

Monocyte-derived, fibroblast-like cells, called fibrocytes, participate in wound-healing and the formation of fibrotic lesions. Aggregated or cross-linked IgG are key effectors in infections, autoimmune diseases, anaphylaxis, and immunotherapy. Cells, including monocytes and fibrocytes, bind IgG using Fc gamma Rs, and aggregated or cross-linked IgG inhibits fibrocyte differentiation. Mice have four different Fc gamma Rs, and which of these, if any, mediate the cross-linked IgG effect on fibrocyte differentiation is unknown. We find that in mice, deletion of Fc gamma RI or the common signaling protein FcR gamma significantly reduces the ability of cross-linked IgG or IgG2a to inhibit fibrocyte differentiation. Cells from Fc gamma RIIb/III/IV KO mice are still sensitive to cross-linked IgG, whereas cells from Fc gamma RI/IIb/III/IV KO mice are insensitive to cross-linked IgG. These observations suggest that IgG-mediated inhibition of fibrocyte differentiation is mediated by Fc gamma Rs, with Fc gamma RI mediating most of the signaling.