863 Blocking the LFA-1 signaling pathway reverses alopecia areata in C3H/HeJ mice

نویسندگان

چکیده

Alopecia areata (AA) is caused by T cell-mediated autoimmune attack of the hair follicle. Therefore, inhibition lymphocyte migration and pathogenic activity represents an attractive therapeutic approach in treatment lymphocyte-mediated diseases, including AA. The function antigen-1 (LFA-1) receptor signaling pathway plays a crucial role cell activation, cells to target tissues formation classical cytolytic immune synapse. We previously showed that intercellular adhesion molecule 1(ICAM-1), one major ligands for LFA-1, upregulated lesional skin both human patients C3H/HeJ mice with observed CD44+CD8+effector/memory expressed high levels LFA-1 within draining lymph nodes as well AA skin. Here, we investigated using mice, found blockade either anti-LFA-1 or anti-ICAM-1 mAbs prevented development grafted mice. Immunohistochemical staining biopsies show anti-LFA-1- anti-ICAM-1-treated have striking decrease infiltration together reduced expression AA-associated markers (MHC-I MHC-II). Furthermore, not only CD44+CD8 +effector/memory into skin, but also led enrichment Tregs nodes. To limit systemic exposure, topically treated lifitegrast, small antagonist lifitegrast was effective reversal Taken together, demonstrated activation AA, achieved local topical delivery. Our results invite further clinical investigation treatment.

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ژورنال

عنوان ژورنال: Journal of Investigative Dermatology

سال: 2022

ISSN: ['1523-1747', '0022-202X']

DOI: https://doi.org/10.1016/j.jid.2022.05.877