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

  • J Invest Dermatol. 2018 Jul;138(7):1555-1563. doi: 10.1016/j.jid.2018.01.036.
Nick Vandeghinste  1 ,  Jürgen Klattig  2 ,  Catherine Jagerschmidt  3 ,  Stéphanie Lavazais  3 ,  Florence Marsais  3 ,  Jan D Haas  2 ,  Marielle Auberval  3 ,  Felix Lauffer  4 ,  Tara Moran  5 ,  Mate Ongenaert  6 ,  Maarten Van Balen  6 ,  Sonia Dupont  3 ,  Liên Lepescheux  3 ,  Teresa Garcia  3 ,  Stefan Härtle  2 ,  Kilian Eyerich  4 ,  Padraic G Fallon  5 ,  Reginald Brys  6 ,  Stefan Steidl  2
Affiliations
  • 1. Galapagos NV, Mechelen, Belgium. Electronic address: [email protected].
  • 2. MorphoSys AG, Planegg, Germany.
  • 3. Galapagos SaSu, Romainville, France.
  • 4. Department of Dermatology and Allergy, University Hospital Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
  • 5. Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
  • 6. Galapagos NV, Mechelen, Belgium.
PMID: 29474945 DOI: 10.1016/j.jid.2018.01.036
Abstract

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.

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