TGF beta activating integrins beta 6 and beta 8 are dysregulated in inflammatory skin disease and cutaneous melanoma

Background: Integrins av beta 6 and av beta 8 are expressed by keratinocytes and transactivate latent TGF beta. In a murine model, integrin mediated activation of TGF beta has been shown to be critical in maintaining skin homeostasis, specifically playing roles in epidermal retention of Langerhans cells and resident memory cells T cells (Trm). Objective: We examine expression of Integrins beta 6 and beta 8 in human skin, inflammatory skin disease, benign nevi, and melanoma and hypothesize that integrin expression is dysregulated in disease. Methods: Using immunohistochemistry, we stained tissue from normal human skin (n = 8), psoriasis (n = 6), atopic dermatitis (n = 6), lichen planus (n = 5), benign nevi (n = 24), and melanoma (n = 25) with anti-integrin beta 6 and anti-integrin beta 8 to survey expression pattern. We also performed a retrospective chart review in the melanoma cohort to examine if integrin beta 6 and beta 8 expression was associated with increased Breslow depth and worse prognostic staging. Results: Here, we show that human keratinocytes express integrins beta 6 and beta 8, similar to murine keratinocytes. We also found that inflammatory skin conditions have increased Integrin beta 6, but not Integrin beta 8 expression. Furthermore, we identified that melanomas have greatly increased expression of integrin beta 8 compared to nevi. Additionally, high expression of integrin beta 8 was correlated with greater Breslow depth at diagnosis and with worse prognostic staging. Conclusion: These findings demonstrate that like murine keratinocytes, human keratinocytes express integrin beta 6 and beta 8 under steady state conditions. Moreover, altered integrin expression may participate in the development or maintenance of cutaneous inflammation as well as tumor immune evasion. (C) 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.