title: A protective role of complement component 3 in T cell-mediated skin inflammation.
abstract: Keratinocytes synthesize complement component 3 (C3) constitutively, and increased expression of C3 has been described during skin inflammation. In this study, we investigated the role of C3 in T cell-mediated allergic contact dermatitis, which is a clinical manifestation of contact sensitivity (CS). C3-deficient mice (C3KO) showed substantial higher CS responses to haptens, inducing a Th1 cytokine-mediated skin inflammation (2,4-dinitrofluorobenzene and dinitrochlorobenzene), and to haptens known to induce a Th2-polarized inflammatory response (fluoro-isothiocynate and toluene-2,4-diisocyanate) as compared to their wild-type (WT) controls. There was a higher influx of GR-1(+) , CD4(+) , and CD8(+) cells into the skin of hapten-treated C3KO mice compared with WT mice. Activated splenocytes from C3KO mice immunized with DNCB secreted higher amounts of IFN-γ compared with WT controls but not of Th2 (IL-4, IL-5, and IL-10) cytokines or IL-17. A higher secretion of IL-12 from splenocytes of C3KO mice as compared with WT mice was observed after TLR-4 ligand (LPS) or TLR-2 ligand (peptidoglycan) stimulation. Thus, an increased expression of IL-12 and of IFN-γ may be responsible for the increased hapten-induced inflammation in C3 deficiency. Finally, we demonstrated that C3KO mice developed oral tolerance to haptens to a lower degree than WT mice. Our findings provide a new insight into a novel anti-inflammatory role of C3 in skin inflammation.
authors.affiliation: Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Ricklinger Strasse 5, Hannover, Germany.
authors.forename: Rahul
authors.initials: R
authors.lastname: Purwar
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bäumer
authors.forename: Margarete
authors.initials: M
authors.lastname: Niebuhr
authors.forename: Thomas
authors.initials: T
authors.lastname: Tschernig
authors.forename: Manfred
authors.initials: M
authors.lastname: Kietzmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000517:prevention & control; D004139:Dinitrofluorobenzene / Q000276:immunology; D006241:Haptens; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D057134:Antibodies, Neutralizing; D003176:Complement C3; D016207:Cytokines; D006241:Haptens; D018664:Interleukin-12; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene