title: Participation of complement 3a receptor (C3aR) in the sensitization phase of Th2 mediated allergic contact dermatitis.
abstract: The complement system has emerged as a bridge between innate and adaptive immune responses. An involvement of C3aR has been described during skin inflammation. The aim of the study was to investigate the role of C3a in a mouse model of allergic skin inflammation, such as allergic contact dermatitis (ACD) which is a clinical manifestation of contact sensitivity (CS). The sensitization phase was studied using the local lymph node test: Mice were sensitized on three consecutive days by application of non-irritant concentrations of toluene-2,4-diisocyanate (TDI; 0.5%) onto the ear skin. On day 5, auricular draining lymph nodes were obtained. The elicitation phase was investigated by sensitization with TDI on the depilated and tape-stripped abdominal skin and challenge with TDI on the ear skin and measuring of ear swelling in vivo and cytokine secretion in activated splenocytes in vitro respectively. Complement 3a receptor deficient (C3aRKO) mice showed increased cytokine responses (interleukin[IL]-5, IL-6, IL-17, granulocyte macrophage-colony stimulating factor [GM-CSF]) in the sensitization phase of ACD to TDI. However, no differences in CS responses to TDI were observed in C3aR KO mice compared with WT controls in the elicitation phase of ACD as assessed by measuring of ear swelling in vivo and cytokines in skin and in activated splenocytes in vitro, namely IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, interferon-γ (IFN-γ), GM-CSF and tumor necrosis factor (TNF)-α. These findings provide a new insight into the participation of C3a in the sensitization phase of CS immune responses.
authors.affiliation: Department of Dermatology and Allergy, Division of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany. niebuhr.margarete@mh-hannover.de
authors.forename: Margarete
authors.initials: M
authors.lastname: Niebuhr
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bäumer
authors.forename: Manfred
authors.initials: M
authors.lastname: Kietzmann
authors.forename: Katja
authors.initials: K
authors.lastname: Wichmann
authors.forename: Annice
authors.initials: A
authors.lastname: Heratizadeh
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011951:Receptors, Complement / Q000378:metabolism*; D018418:Th2 Cells / Q000502:physiology; D014051:Toluene 2,4-Diisocyanate
chemical_list: D016207:Cytokines; D011951:Receptors, Complement; C085567:complement C3a receptor; D014051:Toluene 2,4-Diisocyanate