Neutralization of IL-17C Reduces Skin Inflammation in Mouse Models of Psoriasis and Atopic Dermatitis

作者：Vandeghinste Nick; Klattig Juergen; Jagerschmidt Catherine; Lavazais Stephanie; Marsais Florence; Haas Jan D; Auberval Marielle; Lauffer Felix; Moran Tara; Ongenaert Mate; Van Balen Maarten; Dupont Sonia; Lepescheux Lien; Garcia Teresa; Haertle Stefan; Eyerich Kilian; Fallon Padraic G; Brys Reginald; Steidl Stefan

来源：Journal of Investigative Dermatology, 2018, 138(7): 1555-1563.

DOI：10.1016/j.jid.2018.01.036

IL-17C is a functionally distinct member of the IL-17 family that was believed to play a role in the pathogenesis of psoriasis. Here we confirmed that IL-17C is involved in psoriasis and explored potential roles for IL-17C in atopic dermatitis (AD). An anti-IL-17C antibody, MOR106, was generated that potently and selectively binds to human and mouse IL-17C, thereby inhibiting the binding of IL-17C to its IL-17RE receptor. The antibody inhibited cutaneous inflammation in an IL-23-induced psoriatic-like skin inflammation model. In lesional skin of patients with AD, IL-17C expression levels were increased and localized to keratinocytes and infiltrating immune cells. To determine the contribution of IL-17C to AD pathogenesis, MOR106 was tested in two distinct in vivo models. In the calcipotriol-induced AD model, ear skin inflammation, TSLP, and IL-33 protein production in ears was suppressed by MOR106. Consistently, in the flaky tail strain mouse model, spontaneous development of AD-like skin inflammation was reduced by MOR106. Moreover, serum IgE levels, number of mast cells in skin and T helper type 2-related cytokines IL-4 and CCL17 in serum were all reduced. Overall, our results indicate that IL-17C is a central mediator of skin inflammation beyond psoriasis and is relevant in particular in AD.

• 出版日期2018-7