title: FcγRI is required for TGFβ2-treated macrophage-induced tolerance.
abstract: Macrophages treated with TGFβ2 (TGFβ2-Mϕ) and antigen are highly tolerogenic in vivo, and induce antigen-specific and long-lasting tolerance in both naïve and primed mice via induction of suppressor/regulatory T cells. In this study, we examined the molecular pathways, including the requirements for Smad-dependent signaling, that are involved in the induction and function of tolerogenic TGFβ2-Mϕ. Treatment of murine macrophages with TGFβ2 induced translocation of Smad2/3 to the nucleus, and impairment of Smad3-, but not Smad2-, dependent signaling inhibited the tolerogenic function of a TGFβ2-treated murine macrophage cell line. Gene expression in murine macrophages treated with TGFβ2 was evaluated by microarray analysis. The FcγRI gene was one of a number of immune-related genes differentially expressed in TGFβ2-Mϕ, and appeared to be critical for tolerance in this system, since TGFβ2-Mϕ from FcγRI deficient mice were unable to induce tolerance. The role that FcγRI plays in TGFβ2-Mϕ-mediated tolerance is currently unclear. The results of this study provide important information about the factors that are critical for the induction of TGFβ2-Mϕ-mediated tolerance, and a better understanding of these mechanisms could lead to the development of more effective tolerance-inducing strategies for the treatment of autoimmune/inflammatory diseases.
authors: Department of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA.
authors: Z
authors: Z
authors: Gu
authors: A Y
authors: AY
authors: Chhabra
authors: P
authors: P
authors: Alard
authors: D R
authors: DR
authors: Warner
authors: M M
authors: MM
authors: Kosiewicz
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D046228:Microarray Analysis; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053781:Transforming Growth Factor beta2 / Q000276:immunology*
chemical_list: C485701:Fcgr1 protein, mouse; D017452:Receptors, IgG; D051899:Smad2 Protein; D051900:Smad3 Protein; D053781:Transforming Growth Factor beta2
keywords: ACAID; ANOVA; APC; Antigen presenting cells; CFA; DN; DTH; Delayed type hypersensitivity; FcγR; LPS; Macrophages; Mice; Mϕ; Mϕ59; OVA; PEC; TGFβ; Tolerance; WT; analysis of variance; anterior chamber-associated immune deviation; antigen presenting cells; complete Freund's adjuvant; delayed type hypersensitivity; dominant negative; i.v.; intravenous; lipopolysaccharide; macrophage; macrophage hybridoma cell line; ovalbumin; peritoneal exudates cells; s.c.; subcutaneous; transforming growth factor β; wild-type
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