title: Double-stranded RNA induces inflammation via the NF-κB pathway and inflammasome activation in the outer root sheath cells of hair follicles.
abstract: 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)-1β 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-1β were enhanced. Moreover, NLRP3 knockdown decreased this poly(I:C)-induced IL-1β 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-1β and HMGB1 secretion from ORS cells may contribute to clarifying the pathogenesis and therapeutic targets of AA.
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Shin
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Dae-Kyoung
authors.initials: DK
authors.lastname: Choi
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Min Ha
authors.affiliation: Department of Anatomy, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Ho Lee
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Myung
authors.initials: M
authors.lastname: Im
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Seo
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Chang
authors.initials: C
authors.lastname: Deok Kim
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
mesh_terms: D002461:Cell Line, Transformed; D024243:HMGB1 Protein / Q000276:immunology; D018859:Hair Follicle / Q000276:immunology* / Q000473:pathology; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000276:immunology* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012330:RNA, Double-Stranded; D011070:Poly I-C