Selectively Targeting JAK1 or JAK3 Pathway Is Sufficient to Reverse Alopecia Areata

The study investigated the role of individual Janus kinase (JAK) pathways in treating alopecia areata (AA) using JAK-selective inhibitors in C3H/HeJ mice. It was found that selectively targeting JAK1 with Itacitinib or JAK3 with PF06651600 was effective in reversing AA, as evidenced by decreased skin immune cell infiltration and reduced pathogenic cell responses. In contrast, the JAK2-selective inhibitor CEP33779 did not restore hair regrowth. RNA sequencing data revealed that JAK1 and JAK3 inhibitors normalized gene expression patterns to levels similar to unaffected mice, indicating suppression of the dermal inflammatory/cytotoxic T cell signature. These findings suggested that JAK1 and JAK3 inhibition could be a therapeutic target for AA treatment, while JAK2 inhibition was not necessary for efficacy.