{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:49:58Z","timestamp":1783637398206,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Alopecia areata (AA) is an autoimmune disease caused by T cell-mediated destruction of the hair follicle (HF). Therefore, approaches that effectively disrupt pathogenic T cell responses are predicted to have therapeutic benefit for AA treatment. T cells rely on the duality of T cell receptor (TCR) and gamma chain (\u03b3c) cytokine signaling for their development, activation, and peripheral homeostasis. Ifidancitinib is a potent and selective next-generation JAK1\/3 inhibitor predicted to disrupt \u03b3c cytokine signaling. We found that Ifidancitinib robustly induced hair regrowth in AA-affected C3H\/HeJ mice when fed with Ifidancitinib in chow diets. Skin taken from Ifidancitinib-treated mice showed significantly decreased AA-associated inflammation. CD44<jats:sup>+<\/jats:sup>CD62L<jats:sup>-<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T effector\/memory cells, which are associated with the pathogenesis of AA, were significantly decreased in the peripheral lymphoid organs in Ifidancitinib-treated mice. We observed high expression of co-inhibitory receptors PD-1 on effector\/memory CD8<jats:sup>+<\/jats:sup> T cells, together with decreased IFN-\u03b3 production in Ifidancitinib-treated mice. Furthermore, we found that \u03b3c cytokines regulated T cell exhaustion. Taken together, our data indicate that selective induction of T cell exhaustion using a JAK inhibitor may offer a mechanistic explanation for the success of this treatment strategy in the reversal of autoimmune diseases such as AA.<\/jats:p>","DOI":"10.3389\/fimmu.2022.955038","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T09:41:05Z","timestamp":1663666865000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Induction of T cell exhaustion by JAK1\/3 inhibition in the treatment of alopecia 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