IL-17A as an Inducer for Th2 Immune Responses in Murine Atopic Dermatitis Models

Abstract

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.

A Mouse Model of Anaphylaxis and Atopic Dermatitis to Salt-Soluble Wheat Protein Extract

“…There are variable reports on the role of IL-17 in food allergies, implicating a pathogenic role as well as a marker of food tolerance [27,28]. Nakajima et al [29] proposed a key role for the Th17 pathway in a hapten-induced contact dermatitis mouse model. Our findings of selective elevation of Th17-associated cytokines in wheat protein-induced atopic dermatitis further support the hypothesis of a pathogenic role of elevated Th17 cytokines in food allergy-associated atopic dermatitis.…”

001 IL-17A induces heterogeneous macrophages, and it does not alter the effects of lipopolysaccharides on macrophage activation in the skin of mice

“…However, it has been reported that levels of IL-17A, but not IL-4 and IL-13, is elevated in the skin of Flg ft mice 38 . Thus, Flg ft mice have been used to investigate the effects of IL-17A in skin inflammation 10 . In our study, in addition to the elevated protein expression levels of F4/80, iNOS, CX3CR1 and CD206, both STAT1 and STAT3 were activated in the skin of Flg ft mice.…”

“…The roles of IL-17A are also implicated in the pathogenesis of AD 7,8 . IL-17A is highly expressed in flaky-tail (Flg ft ) mouse, a murine AD model, that carries mutations in the filaggrin gene 9,10 To clarify whether macrophages act as effectors of Th17 immunity, we investigated the effects of IL-17A injection on the macrophage activation in the skin of B6 wild-type mice. Lipopolysaccharides (LPS) is known to activate macrophages via Toll-like receptor 4 (TLR4) related classical pathway.…”

“…The roles of IL-17A are also implicated in the pathogenesis of AD 7,8 . IL-17A is highly expressed in flaky-tail (Flg ft ) mouse, a murine AD model, that carries mutations in the filaggrin gene 9,10 . Moreover, IL-17A is involved in infectious, inflammatory, neutrophilic, granulomatous, bullous and malignant skin diseases 11 .…”

Biological Therapeutic Treatment of Atopic Dermatitis

“…Известно, что ИЛ-25 (ИЛ-17Е), один из представителей семейства ИЛ-17, способствует активации Th2-клеток и поврежде-нию синтеза филаггрина кератиноцитами [64,65]. В то же время роль Th17 Т-лимфоцитов в патогенезе АД до конца не ясна и требует дальнейшего изучения [66]. Пролифе-рация Th2 Т-клеток приводит к повышенной экспрессии ИЛ-4, ИЛ-5, ИЛ-13, ИЛ-31.…”