Pilling Darrell, Crawford Jeffrey R, Verbeek J Sjef, Gomer Richard H
Department of Biology, Texas A&M University, College Station, Texas, USA;
Department of Biology, Texas A&M University, College Station, Texas, USA; Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, USA; and.
J Leukoc Biol. 2014 Aug;96(2):275-82. doi: 10.1189/jlb.3AB0913-490RR. Epub 2014 Apr 21.
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 FcγRs, and aggregated or cross-linked IgG inhibits fibrocyte differentiation. Mice have four different FcγRs, and which of these, if any, mediate the cross-linked IgG effect on fibrocyte differentiation is unknown. We find that in mice, deletion of FcγRI or the common signaling protein FcRγ significantly reduces the ability of cross-linked IgG or IgG2a to inhibit fibrocyte differentiation. Cells from FcγRIIb/III/IV KO mice are still sensitive to cross-linked IgG, whereas cells from FcγRI/IIb/III/IV KO mice are insensitive to cross-linked IgG. These observations suggest that IgG-mediated inhibition of fibrocyte differentiation is mediated by FcγRs, with FcγRI mediating most of the signaling.
单核细胞衍生的成纤维细胞样细胞,即纤维细胞,参与伤口愈合和纤维化病变的形成。聚集或交联的IgG是感染、自身免疫性疾病、过敏反应和免疫治疗中的关键效应因子。包括单核细胞和纤维细胞在内的细胞通过FcγR结合IgG,而聚集或交联的IgG会抑制纤维细胞分化。小鼠有四种不同的FcγR,其中哪一种(如果有的话)介导交联IgG对纤维细胞分化的作用尚不清楚。我们发现,在小鼠中,FcγRI或共同信号蛋白FcRγ的缺失显著降低了交联IgG或IgG2a抑制纤维细胞分化的能力。来自FcγRIIb/III/IV基因敲除小鼠的细胞对交联IgG仍敏感,而来自FcγRI/IIb/III/IV基因敲除小鼠的细胞对交联IgG不敏感。这些观察结果表明,IgG介导的纤维细胞分化抑制是由FcγR介导的,其中FcγRI介导了大部分信号传导。