%0 Journal Article
%T An OX-Tra'Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis.
%A Sadrolashrafi K
%A Guo L
%A Kikuchi R
%A Hao A
%A Yamamoto RK
%A Tolson HC
%A Bilimoria SN
%A Yee DK
%A Armstrong AW
%J Cells
%V 13
%N 7
%D 2024 Mar 28
%M 38607026
%F 7.666
%R 10.3390/cells13070587
%X The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management.