Double-stranded RNA induces inflammation via the NF-kappa B pathway and inflammasome activation in the outer root sheath cells of hair follicles

作者：Shin Jung Min; Choi Dae Kyoung; Sohn Kyung Cheol; Kim Soo Yeon; Ha Jeong Min; Lee Young Ho; Im Myung; Seo Young Joon; Kim Chang Deok; Lee Jeung Hoon; Lee Young

来源：Scientific Reports, 2017, 7(1): 44127.

DOI：10.1038/srep44127

Alopecia areata (AA), a chronic, relapsing, hair-loss disorder, is considered to be a T cell-mediated autoimmune disease. It affects approximately 1.7% of the population, but its precise pathogenesis remains to be elucidated. Despite the recent attention focused on the roles of inflammasomes in the pathogenesis of autoinflammatory diseases, little is known about inflammasome activation in AA. Thus, in this study, we investigated the pattern of NLRP3 inflammasome activation in the outer root sheath (ORS) cells of hair follicles. We found that interleukin (IL)-1 beta and caspase-1 expression was increased in hair follicle remnants and inflammatory cells of AA tissue specimens. After stimulation of ORS cells with the double-stranded (ds) RNA mimic polyinosinic: polycytidylic acid (poly[I:C]), the activation of caspase-1 and secretion of IL-1 beta were enhanced. Moreover, NLRP3 knockdown decreased this poly(I:C)induced IL-1 beta production. Finally, we found that high-mobility group box 1 (HMGB1) translocated from the nucleus to the cytosol and was secreted into the extracellular space by inflammasome activation. Taken together, these findings suggest that ORS cells are important immunocompetent cells that induce NLRP3 inflammasomes. In addition, dsRNA-induced IL-1 beta and HMGB1 secretion from ORS cells may contribute to clarifying the pathogenesis and therapeutic targets of AA.

• 出版日期2017-3-7