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Interleukin-26 potentiates type 2 skin inflammation in presence of interleukin-1β

Bier, Katharina, Senajova, Zuzana, Henrion, Fanny, Wang, Yichen, Bruno, Sandro, Rauld, Celine, Hoermann, Lisa, Barske, Carmen, Delucis-Bronn, Corinne, Bergling, Sebastian, Altorfer, Marc, Haegele, Jasmin, Knehr, Judith, Junt, Tobias, Roediger, Ben, Roehn, Till and Kolbinger, Frank (2023) Interleukin-26 potentiates type 2 skin inflammation in presence of interleukin-1β. Interleukin-26 potentiates type 2 skin inflammation in presence of interleukin-1β.

Abstract

Atopic dermatitis (AD) is a debilitating inflammatory skin disorder. Biologics targeting the IL-4/IL-13 axis are effective in AD, but there is still a large proportion of patients that do not respond to IL-4R blockade. Further exploration of potentially pathogenic T cell-derived cytokines in AD may lead to new effective treatments. This study aimed to investigate the downstream effects of IL-26 on skin in the context of type 2 skin inflammation. We found that IL-26 alone exhibited limited inflammatory activity in skin. However, in presence of IL-1β, IL-26 potentiated the secretion of TSLP, CXCL1 and CCL20 from human epidermis through JAK/STAT signaling. Moreover, in an in vivo AD-like skin inflammation model, IL-26 exacerbated skin pathology and locally increased type 2 cytokines, most notably of Il13 in skin T helper cells. Neutralization of IL-1β abrogated IL-26-mediated effects, indicating that the presence of IL-1β is required for full IL-26 downstream action in vivo. These findings suggest that the presence of IL-1β enables IL-26 to be a key amplifier of inflammation in the skin. As such, IL-26 may contribute to the development and pathogenesis of inflammatory skin disorders such as AD.

Item Type: Article
Keywords: IL-26, atopic dermatitis, type 2 skin inflammation, MC903 model, S. aureus
Date Deposited: 12 Mar 2024 00:46
Last Modified: 12 Mar 2024 00:46
URI: https://oak.novartis.com/id/eprint/52147

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