The crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areata

Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFN? and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFN? and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFN? and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.

Automated summary

Alopecia areata (AA) is a T-cell-mediated autoimmune disease causing chronic hair loss, with its exact pathogenesis still unclear. Recent studies have shown the importance of crosstalk between inflammasomes and mitophagy, a process that removes damaged mitochondria. This study found mitochondrial DNA damage in AA-affected scalp tissues and treated cells, as well as increased mitochondrial reactive oxygen species (ROS) levels with treatment. Mitophagy induction was shown to alleviate NLRP3 inflammasome activation, and PINK1-mediated mitophagy played a critical role in inflammasome activation. These findings highlight the significance of mitophagy-inflammasome crosstalk in AA pathogenesis and suggest potential therapeutic targets.