20.500.12556/DiRROS-25206 Activation of α2B/2C adrenergic receptor ameliorates ocular surface inflammation through enhancing regulatory T cell function There is an unmet need for effectively treating dry eye disease (DED), a T cell-mediated chronic, inflammatory ocular surface disorder. Given the potential of nonneuronal adrenergic system in modulating T cell response, we herein investigated the therapeutic efficacy and the underlying mechanisms of a specific alpha 2 adrenergic receptor agonist (AGN-762, selective for α2B/2C receptor subtypes) in a mouse model of DED. Experimental DED was treated with the AGN-762 by oral gavage, either at disease induction or after disease establishment, and showed sustained amelioration, along with reduced expression of DED-pathogenic cytokines in ocular surface tissues, decreased corneal MHC-II+CD11b+cells and lymphoid Th17 cells, and higher function of regulatory T cells (Treg). In vitro culture of DED- derived effector T helper cells (Teff) with AGN-762 failed to suppress Th17 response, while culture of DED-Treg with AGN-762 led to enhanced suppressive function of Treg and their IL-10 production. Adoptive transfer of AGN-762-pretreated DED-Treg in syngeneic B6.Rag1-/- mice effectively suppressed DED Teff-mediated disease and Th17 response, and the effect was abolished by the neutralization of IL-10. In conclusion, our findings demonstrate that α2B/2C adrenergic receptor agonism effectively ameliorates persistent corneal epitheliopathy in DED by enhancing IL-10 production from Treg and thus restoring their immunoregulatory function. dry eye disease treatment T cells Th17 immunity autoimmunity true false true Angleški jezik Ni določen Neznano 2026-01-13 15:15:44 2026-01-13 15:15:44 2026-01-14 03:53:46 0000-00-00 00:00:00 2024 0 0 str. 176-187 issue 1 Vol. 18 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 617.7 1933-0219 10.1016/j.mucimm.2024.11.002 220814595 RAZ_Fan_Nai-Wen_2024.pdf RAZ_Fan_Nai-Wen_2024.pdf 1 F8C0B2DBD0E4BED75DD4621D32736B5D 3c797391bde917c0093209ab9f13989719edaed5ee864bf0719ac985eaae5676 8972a450-f08a-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=38024 https://www.mucosalimmunology.org/article/S1933-0219(24)00110-7/ 0 5aa16869-f08a-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=38023 Univerzitetni klinični center Ljubljana 0 0 0