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bioRxiv · 10.1101/2025.05.07.650678

Th1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata

Abstract

Alopecia areata (AA) is an autoimmune disease that is clinically characterized by hair loss and histologically by a peribulbar infiltrate of CD8 and CD4 T cells. Prior studies have focused on the role of CD8 T cells in the development of AA; however, the role of CD4 T cells remains unclear. Here, we demonstrate that CD4 T cells from the skin draining lymph nodes (SDLN) of AA mice transferred disease into recipient mice. Further, these cells exhibited a T-helper type 1 (Th1) effector transcriptional and phenotypic profile. The pathogenic activity of these CD4 T cells was dependent upon the presence of endogenous CD8 T cells and host IFN-{gamma} responsiveness. Targeted deletion of CD4 T cell-mediated production of IFN-{gamma} abrogated the ability of this cell population to transfer disease. Together, these data provide mechanistic insights into pathways that lead to AA development, strengthening our understanding of the disease and inviting studies into exploring novel therapeutic strategies for human patients.

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Connell, S. J., Crotts, S., Reis, R., Lensing, M., Kahl, P., Henderson, N., Ayush, O., Zhu, Z., Ortolan, L. S., Harty, J., Goverman, J., Jabbari, A.. 2025-05-07. Th1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata. https://doi.org/10.1101/2025.05.07.650678

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