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: Rahul Purwar, Wolfgang Bäumer, Margarete Niebuhr, Thomas Tschernig, Manfred Kietzmann, Thomas Werfel
• Journal: Experimental dermatology (Exp Dermatol) Vol. 20 Issue 9 Pg. 709-14 (Sep 2011) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 21569105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Antibodies, Neutralizing
• Complement C3
• Cytokines
• Haptens
• Interleukin-12
• Interferon-gamma
• Dinitrofluorobenzene

Topics

• Animals
• Antibodies, Neutralizing
• CD4-Positive T-Lymphocytes (immunology, pathology)
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Complement C3 (antagonists & inhibitors, deficiency, genetics, immunology)
• Cytokines (metabolism)
• Dermatitis, Allergic Contact (immunology, prevention & control)
• Dinitrofluorobenzene (immunology)
• Haptens
• Immune Tolerance
• Interferon-gamma (biosynthesis)
• Interleukin-12 (biosynthesis)
• Mice
• Mice, Knockout
• Neutrophils (immunology, pathology)
• Skin (immunology, pathology)
• Spleen (immunology, pathology)
• T-Lymphocytes (immunology, pathology)