IL-26 Potentiates Type 2 Skin Inflammation in the Presence of IL-1β
Journal of Investigative Dermatology, 2024
Bier K., Senajova Z., Henrion F., Wang Y., Bruno S., Rauld C., Hörmann L., Barske C., Delucis-Bronn C., Bergling S., Altorfer M., Hägele J., Knehr J., Junt T., Roediger B., Röhn T., Kolbinger F.
Disease area | Application area | Sample type | Products |
---|---|---|---|
Dermatological Diseases | Pathophysiology | Cell Culture Supernatant | Olink Target 96 |
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.