513 NLRP3-dependent innate cytokine IL-1β in keratinocytes promotes immune response of CD4 and CD8 T cells in vitiligo patients

Abstract

Background: Vitiligo is associated with increased reactive oxygen species (ROS) leveland the oxidative stress-induced activation of melanocyte-specific autoimmunity. The NLR family pyrin domain containing 3 (NLRP3) inflammasome plays a key role in oxidative stress-driven undesirable immune response. However, the role of NLRP3 inflammasome in vitiligo immune response is not clear. Methods: We first detected NLRP3 inflammasome proteins and activation in perilesions and serum of patients with vitiligo, as well as in keratinocytes exposed to H2O2. Next, we tested the migration, activation and cytokines production of CD4+ and CD8+ T cells from patients with vitiligo mediated by NLRP3 inflammasome using flow cytomey and ELISA. Results: The expressions of NLRP3 and downstream cytokine IL-1β were elevated in perilesional specimens from vitiligo patients. Meanwhile, serum IL-1β level was increased in vitiligo patients, correlated with disease activity and decreased after combined therapy with Diprospan, narrow band-UVB and topical Tacrolimus. Furthermore, we found that keratinocyte-derived IL-1β could increase CXCL16 and CXCL10 expression predominantly through NF-κB and IRF1 pathway in absence of IFN-γ, thus promote the migration ability of circulating CD8+ T cells. Moreover, keratinocyte-derived IL-1β promoted the Th1 and Th17 cytokinesproduction of CD8+ and CD4+T cells through the IL-1R signaling. Conclusion: Our study demonstrated that NLRP3 inflammasome is activated in vitiligo keratinocytes, and the innate cytokine IL-1β promotes CD8+T-cell skin migration, Th1 and Th17 cytokines production and thereby contributes to immune response in patients with vitiligo.