Products Cited in Publications Worldwide NLRP3 autophagic degradation disruption in melanocytes contributes to vitiligo development

NLRP3 autophagic degradation disruption in melanocytes contributes to vitiligo development

Zeng, Ke; Zhu, Yuqi; Han, Zhongxin; Xiong, Siyi; Zhao, Yan; Xiao, Zilong; Xie, Yingchao; Jin, Shiyu; Dong, Tingru; Lan, Lan

DOI: PMID:

Abstract

NLRP3 functions as a critical intracellular danger sensor for inflammasome activation, playing a crucial role in autoimmune diseases. Vitiligo progression has been linked to NLRP3, yet its specific involvement in melanocytes of vitiligo remains poorly understood. In this study, we demonstrate that NLRP3 expression is significantly upregulated in the melanocytes of vitiligo patients and melanoma-Treg-induced vitiligo mouse model. Genetic knockout of NLRP3 effectively alleviates vitiligo progression in these mice. Our mechanistic investigations reveal that the downregulation of the E3 ligase β-TrCP1 in vitiligo melanocytes decreases K27-linked ubiquitination levels of NLRP3, which in turn weakens its interaction with the receptor NDP52. This disruption impairs the selective autophagic degradation of NLRP3, leading to hyperactivation of inflammation and in melanocytes, thereby accelerating vitiligo pathogenesis. Notably, melanocyte-specific knockdown of NLRP3 using lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos) carrying Nlrp3 shRNA significantly alleviates vitiligo development. This study elucidates the mechanism by which dysfunction mediated excessive NLRP3 inflammasome activation in melanocytes contributes to vitiligo pathogenesis, highlighting potential therapeutic strategies targeting these pathways for the treatment of vitiligo and other pigment-related skin diseases.

Purchased from AmBeed

MG-132

A181909133407-82-698%

MG-132

191.0/50mg

Detail