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02.11 Il-38 is not involved in the modulation of imq-induced skin inflammation
  1. Jennifer Palomo,
  2. Sabina Troccaz,
  3. Emiliana Rodriguez,
  4. Dominique Talabot-Ayer,
  5. Cem Gabay,
  6. Gaby Palmer
  1. Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, and Department of Pathology and Immunology, University of Geneva, School of Medicine, Geneva, Switzerland

Abstract

Background Psoriasis is a common chronic skin disorder caused by a dysregulated crosstalk between immune and resident cells (eg, keratinocytes). The identification of the pathogenic role of several cytokines in psoriasis led to the development of successful therapies. Recently, IL-36 cytokines, which belong to the IL-1 family, were shown to be involved in the pathogenesis of psoriasis. Mice deficient in IL-36 receptor (IL-36R) were protected from imiquimod (IMQ)-induced skin inflammation, whereas IL-36R antagonist (IL-36Ra) KO mice exhibited a more severe phenotype. The objective of our study was to examine the expression and function of IL-38, a newly discovered IL-1 family member with supposed IL-36 inhibitory properties, in the IMQ model of psoriasis.

Materials and methods IL-38 mRNA expression was determined in skin samples, at steady state or after IMQ application. IL-38 KO or IL-36Ra KO mice and their respective WT littermates were challenged with the topical application of IMQ on the left ear during 7 days. The severity of skin inflammation was assessed by daily measurement of ear thickness using a calliper, by semi-quantitative histologic scoring, and by measuring mRNA levels of inflammatory markers.

Results At the peak of IMQ-induced skin inflammation, IL-38 mRNA levels were lower than in normal skin, whereas IL-36Ra mRNA levels were increased in IMQ treated skin. The severity of skin inflammation, as assessed by ear thickness, histological changes (leukocyte infiltration and epidermis hyperplasia) and pro-inflammatory mediator transcript levels, was not significantly different in IL-38 KO and WT mice. After cessation of topical IMQ application, the resolution of skin inflammation was also not altered by IL-38 deficiency. As opposed to these findings, IL-36Ra deficient mice displayed more severe pathological changes as compared to WT mice.

Conclusions We showed that endogenous IL-38 is not involved in the development and the resolution of IMQ-induced skin inflammation. Our findings suggest that IL-38 does not exert IL-36 inhibitory activities in the skin.

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