IL-17A as an inducer for Th2 immune responses in murine atopic dermatitis models.
Atopic dermatitis (AD) is generally regarded as a type 2 helper T (Th2)-mediated inflammatory skin disease. Although the number of IL-17A-producing cells is increased in the peripheral blood and in acute skin lesion of AD patients, the role of IL-17A in the pathogenesis of AD remains unclear. To clarify this issue, we used murine AD models in an IL-17A-deficient condition. In a repeated hapten application-induced AD model, skin inflammation, IL-4 production in the draining lymph nodes (LNs), and hapten-specific IgG1 and IgE induction were suppressed in IL-17A-deficient mice. Vγ4(+) γδ T cells in the skin-draining LNs and Vγ5(-) dermal γδ T cells in the skin were the major sources of IL-17A. Consistently, in flaky-tail (Flg(ft/ft) ma/ma) mice, spontaneous development of AD-like dermatitis and IgE induction were attenuated by IL-17A deficiency. Moreover, Th2 differentiation from naive T cells was promoted in vitro by the addition of IL-17A. Taken together, our results suggest that IL-17A mediates Th2-type immune responses and that IL-17A signal may be a therapeutic target of AD.
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Saeko
S
Nakajima
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Akihiko
A
Kitoh
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Gyohei
G
Egawa
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Dermatology, Kurume University School of Medicine, Kurume, Japan.
Yohei
Y
Natsuaki
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Satoshi
S
Nakamizo
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Catharina Sagita
CS
Moniaga
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Atsushi
A
Otsuka
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tetsuya
T
Honda
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Sho
S
Hanakawa
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Wataru
W
Amano
Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yoichiro
Y
Iwakura
Department of Medical Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
Susumu
S
Nakae
Division of Molecular Pathology, Research Institute for Biological Science, Tokyo University of Science, Chiba, Japan.
Masato
M
Kubo
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Yoshiki
Y
Miyachi
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: kaba@kuhp.kyoto-u.ac.jp.
Kenji
K
Kabashima
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000209:etiology / Q000276:immunology*; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000096:biosynthesis; D020381:Interleukin-17 / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D018925:Chemokines; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4; D007073:Immunoglobulin E