title: CXCR3 deficiency prolongs Th1-type contact hypersensitivity.
abstract: Sensitization and challenge using dinitrofluorobenzene (DNFB) induce contact hypersensitivity (CHS) with Th1 cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. In this study, we attempted to determine the role of CXCR3, a chemokine receptor, in Th1- and Th2-type CHS induced by DNFB or FITC using CXCR3-deficient (CXCR3(-/-)) mice. Ear swelling was prolonged after DNFB challenge in CXCR3(-/-) mice, which was accompanied by increased Th1 cytokines and decreased TGF-β and IL-10 expression at a late time point of CHS, whereas there was no significant difference between wild-type and CXCR3(-/-) mice in FITC-induced CHS. In Th1-type CHS, the number of regulatory T cells (Tregs) was decreased in the challenged ear of CXCR3(-/-) mice compared with that of wild-type mice, suggesting that CXCR3 would be important in migration of Tregs into the site of inflammation. Moreover, we examined the characteristics of CXCR3(+) Tregs both in vitro and in vivo, revealing that CXCR3(+) Tregs expressed high levels of TGF-β and IL-10 as well as IFN-γ compared with CXCR3(-) Tregs. When CXCR3(-/-) mice were injected with CXCR3(+) Tregs, the prolonged ear swelling induced by DNFB was normalized. Taken together, our results suggest that CXCR3(+) Tregs play a key role for quenching Th1-type CHS.
authors: Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors: Hiraku
authors: H
authors: Suga
authors: Makoto
authors: M
authors: Sugaya
authors: Tomomitsu
authors: T
authors: Miyagaki
authors: Hanako
authors: H
authors: Ohmatsu
authors: Hitoshi
authors: H
authors: Okochi
authors: Shinichi
authors: S
authors: Sato
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D016650:Fluorescein-5-isothiocyanate / Q000633:toxicity; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007509:Irritants / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054367:Receptors, CXCR3 / Q000172:deficiency / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: C515188:Cxcr3 protein, mouse; D007509:Irritants; D054367:Receptors, CXCR3; D004139:Dinitrofluorobenzene; D016650:Fluorescein-5-isothiocyanate