title: Thymic stromal lymphopoietin-induced interleukin-17A is involved in the development of IgE-mediated atopic dermatitis-like skin lesions in mice.
abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with elevated levels of allergen-specific IgE. Although thymic stromal lymphopoietin (TSLP) and interleukin-17A (IL-17A) have been considered as important factors in allergic diseases, their relationships in AD have not been fully defined. Here, we show the contribution of TSLP-induced IL-17A responses to IgE-mediated AD-like skin lesions. BALB/c mice passively sensitized by intraperitoneal injections of ovalbumin (OVA)-specific IgE monoclonal antibody (mAb) were challenged with OVA applied to the skin six times. Treatment with anti-TSLP mAb during the second to sixth challenges inhibited IgE-mediated AD-like skin lesions and IL-17A production in lymph nodes. Furthermore, the increased number of IL-17A-producing CD4(+) and γδ T cells in lymph nodes and neutrophilic inflammation in the skin were reduced by anti-TSLP mAb. These findings prompted us to examine the roles of IL-17A. Treatment with anti-IL-17A mAb suppressed the AD-like skin lesions and neutrophilic inflammation; anti-Gr-1 mAb also inhibited them. Furthermore, treatment with CXCR2 antagonist reduced the AD-like skin lesions and neutrophilic inflammation accompanied by the reduction of IL-17A production; the increased CXCR2 expression in the epidermal cells was suppressed by anti-TSLP mAb. Meanwhile, these treatments, except for anti-Gr-1 mAb, inhibited the increased mast cell accumulation in the skin. Collectively, the mechanism of IgE mediating IL-17A-producing CD4(+) and γδ T cells through TSLP by repeated antigen challenges is involved in AD-like skin lesions associated with skin inflammation, such as neutrophil and mast cell accumulation; TSLP may regulate CXCR2 signalling-induced IL-17A production.
authors: Department of Pharmacology, Kobe Pharmaceutical University, Higashinada, Kobe, Japan.
authors: Nobuaki
authors: N
authors: Mizutani
authors: Department of Pharmacology, Kobe Pharmaceutical University, Higashinada, Kobe, Japan.|Nutraceutical and Functional Food Research and Development Centre, Prince of Songkla University, Hat-Yai, Songkhla, Thailand.
authors: Chutha
authors: C
authors: Sae-Wong
authors: Department of Pharmacology, Kobe Pharmaceutical University, Higashinada, Kobe, Japan.
authors: Sureeporn
authors: S
authors: Kangsanant
authors: Department of Pharmacology, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan.|Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors: Takeshi
authors: T
authors: Nabe
authors: Department of Pharmacology, Kobe Pharmaceutical University, Higashinada, Kobe, Japan.
authors: Shin
authors: S
authors: Yoshino
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology*; D016130:Immunophenotyping; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D016207:Cytokines; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023063:Receptors, Interleukin-8B; D007073:Immunoglobulin E; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: IgE; atopic dermatitis; interleukin-17A; mast cells; neutrophils; thymic stromal lymphopoietin