| Title: | Activation of α2B/2C adrenergic receptor ameliorates ocular surface inflammation through enhancing regulatory T cell function |
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| Authors: | ID Fan, Nai-Wen (Author)
ID Yu, Man (Author)
ID Wang, Shudan (Author)
ID Blanco, Tomas (Author)
ID Lužnik Marzidovšek, Zala (Author)
ID Chauhan, Sunil K. (Author)
ID Viswanath, Veena (Author)
ID Gil, Daniel (Author)
ID Held, Katherine S (Author)
ID Chen, Yihe (Author)
ID Reza, Dana (Author) |
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| Files: |  PDF - Presentation file, download (7,14 MB)
MD5: F8C0B2DBD0E4BED75DD4621D32736B5D
 URL - Source URL, visit https://www.mucosalimmunology.org/article/S1933-0219(24)00110-7/
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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| Abstract: | 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. |
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| Keywords: | dry eye disease, treatment, T cells, Th17 immunity, autoimmunity |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2024 |
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| Number of pages: | str. 176-187 |
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| Numbering: | Vol. 18, issue 1 |
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| PID: | 20.500.12556/DiRROS-25206  |
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| UDC: | 617.7 |
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| ISSN on article: | 1933-0219 |
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| DOI: | 10.1016/j.mucimm.2024.11.002 |
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| COBISS.SI-ID: | 220814595 |
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| Note: |
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| Publication date in DiRROS: | 13.01.2026 |
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| Views: | 153 |
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| Downloads: | 78 |
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