title: Inhibition of murine fibrocyte differentiation by cross-linked IgG is dependent on FcγRI.
abstract: 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.
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, USA;
authors.forename: Darrell
authors.initials: D
authors.lastname: Pilling
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, USA; Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, USA; and.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Crawford
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J Sjef
authors.initials: JS
authors.lastname: Verbeek
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, USA; Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, USA; and rgomer@tamu.edu.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gomer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007152:Immunologic Capping; D051379:Mice; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: C485701:Fcgr1 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG
keywords: CD64; FcRγ; SAP; monocyte; pentraxin
references.citation: Hum Pathol. 2010 May;41(5):672-8
references.pmid: 20040395
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18284-9
references.pmid: 17114286
references.citation: J Immunol. 2003 Nov 15;171(10):5537-46
references.pmid: 14607961
references.citation: Nat Immunol. 2007 Jul;8(7):762-71
references.pmid: 17558411
references.citation: J Exp Med. 1992 Aug 1;176(2):469-75
references.pmid: 1386873
references.citation: J Immunol. 2011 Aug 1;187(3):1304-13
references.pmid: 21724994
references.citation: J Immunol Methods. 2010 Dec 15;363(1):9-20
references.pmid: 20888336
references.citation: Science. 2009 Jul 31;325(5940):612-6
references.pmid: 19644120
references.citation: Sci Transl Med. 2009 Nov 4;1(5):5ra13
references.pmid: 20368175
references.citation: J Leukoc Biol. 2012 Oct;92(4):699-711
references.pmid: 22493081
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17892-7
references.pmid: 19815530
references.citation: J Leukoc Biol. 2006 Jun;79(6):1242-51
references.pmid: 16543402
references.citation: PLoS Biol. 2004 Aug;2(8):E243
references.pmid: 15314659
references.citation: Wound Repair Regen. 2007 Sep-Oct;15 Suppl 1:S18-26
references.pmid: 17727462
references.citation: J Clin Invest. 2004 Aug;114(3):438-46
references.pmid: 15286810
references.citation: PLoS One. 2009 Oct 16;4(10):e7475
references.pmid: 19834619
references.citation: Immunity. 2013 Jan 24;38(1):79-91
references.pmid: 23273845
references.citation: Nat Immunol. 2009 Apr;10(4):340-7
references.pmid: 19295630
references.citation: Immunity. 2004 Dec;21(6):769-80
references.pmid: 15589166
references.citation: J Leukoc Biol. 2008 Jun;83(6):1323-33
references.pmid: 18332234
references.citation: Mol Med. 1994 Nov;1(1):71-81
references.pmid: 8790603
references.citation: Nat Rev Immunol. 2008 Jan;8(1):34-47
references.pmid: 18064051
references.citation: J Immunol Methods. 2009 Dec 31;351(1-2):62-70
references.pmid: 19818792
references.citation: PLoS One. 2012;7(9):e45674
references.pmid: 23029177
references.citation: Immunity. 1996 Aug;5(2):181-8
references.pmid: 8769481
references.citation: Nat Rev Immunol. 2011 Jun;11(6):427-35
references.pmid: 21597472
references.citation: Biochem Biophys Res Commun. 2007 Feb 2;353(1):104-8
references.pmid: 17174272
references.citation: Blood. 2012 Jun 14;119(24):5640-9
references.pmid: 22535666
references.citation: J Leukoc Biol. 2007 Sep;82(3):449-56
references.pmid: 17550974
references.citation: J Hepatol. 2006 Sep;45(3):429-38
references.pmid: 16846660
references.citation: J Immunol. 2001 Jun 15;166(12):7556-62
references.pmid: 11390511
references.citation: Wound Repair Regen. 2005 Jul-Aug;13(4):398-404
references.pmid: 16008729
references.citation: Immunity. 2002 Mar;16(3):391-402
references.pmid: 11911824
references.citation: Immunity. 2006 Jan;24(1):19-28
references.pmid: 16413920
references.citation: J Immunol. 2007 Sep 15;179(6):4035-44
references.pmid: 17785842
references.citation: J Clin Invest. 2008 Nov;118(11):3738-50
references.pmid: 18949059
references.citation: Genes Immun. 2006 Oct;7(7):592-9
references.pmid: 16943797
references.citation: Immunity. 2011 Dec 23;35(6):932-44
references.pmid: 22169040
references.citation: Immunology. 2004 Jun;112(2):255-64
references.pmid: 15147569
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10179-84
references.pmid: 18632582