IL-1 Receptor–Knockout Mice Develop Epidermal Cysts and Show an Altered Innate Immune Response after Exposure to UVB Radiation

• DOI: 10.1016/j.jid.2017.07.814
• Publication Date: 2017-07-26T02:45:15Z
• Authors: Nikhil N. Kulkarni; Christopher A. Adase; Ling-juan Zhang; Andrew W. Borkowski; Fengwu Li; James A. Sanford; Daniel J. Coleman; Carlos Aguilera; Arup K. Indra; Richard L. Gallo
• Keywords: Proinflammatory cytokine; Keratin 5; Knockout mouse

In this study, we observed that mice lacking the IL-1 receptor (IL-1R) (IL1r-/-) or deficient in IL1-β developed multiple epidermal cysts after chronic UVB exposure. Cysts that developed in IL1r-/- mice were characterized by the presence of the hair follicle marker Sox 9, keratins 10 and 14, and normal melanocyte distribution and retinoid X receptor-α expression. The increased incidence of cysts in IL1r-/- mice was associated with less skin inflammation as characterized by decreased recruitment of macrophages, and their skin also maintained epidermal barrier function compared with wild-type mice. Transcriptional analysis of the skin of IL1r-/- mice after UVB exposure showed decreased gene expression of proinflammatory cytokines such as tumor necrosis factor-α and IL-6. In vitro, primary keratinocytes derived from IL1r-/- mice were more resistant to UVB-triggered cell death compared with wild-type cells, and tumor necrosis factor-α release was completely blocked in the absence of IL-1R. These observations illustrate an unexpected yet prominent phenotype associated with the lack of IL-1R signaling in mice and support further investigation into the role of IL-1 ligands in epidermal repair and innate immune response after damaging UVB exposure.