The Effect of JAK Inhibitor on the Survival, Anagen Re-Entry, and Hair Follicle Immune Privilege Restoration in Human Dermal Papilla Cells.

ABSTRACT: Topical or systemic administration of JAK inhibitors has been shown to be a new treatment modality for severe alopecia areata (AA). Some patients show a good response to JAK inhibitors, but frequently relapse after cessation of the treatment. There have been no guidelines about the indications and use of JAK inhibitors in treating AA. The basic pathomechanism of AA and the relevant role of JAK inhibitors should support how to efficiently use JAK inhibitors. We sought to investigate the effect of JAK1/2 inhibitor on an in vitro model of AA and to examine the possible mechanisms. We used interferon gamma-pretreated human dermal papilla cells (hDPCs) as an in vitro model of AA. Ruxolitinib was administered to the hDPCs, and cell viability was assessed. The change of expression of the Wnt/?-catenin pathway, molecules related to the JAK-STAT pathway, and growth factors in ruxolitinib-treated hDPCs was also examined by reverse transcription PCR and Western blot assay. We examined immune-privilege-related molecules by immunohistochemistry in hair-follicle culture models. Ruxolitinib did not affect the cell viability of the hDPCs. Ruxolitinib activated several molecules in the Wnt/?-catenin signaling pathway, including Lef1 and ?-catenin, and suppressed the transcription of DKK1 in hDPCs, but not its translation. Ruxolitinib reverted IFN-?-induced expression of caspase-1, IL-1?, IL-15, and IL-18, and stimulated several growth factors, such as FGF7. Ruxolitinib suppressed the phosphorylation of JAK1, JAK2 and JAK3, and STAT1 and 3 compared to IFN-? pretreated hDPCs. Ruxolitinib pretreatment showed a protective effect on IFN-?-induced expression of MHC-class II molecules in cultured hair follicles. In conclusion, ruxolitinib modulated and reverted the interferon-induced inflammatory changes by blocking the JAK-STAT pathway in hDPCs under an AA-like environment. Ruxolitinib directly stimulated anagen-re-entry signals in hDPCs by affecting the Wnt/?-catenin pathway and promoting growth factors in hDPCs. Ruxolitinib treatment prevented IFN-?-induced collapse of hair-follicle immune privilege.

SUBMITTER: Kim JE 

PROVIDER: S-EPMC7404120 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature