S100A8/A9 Promotes Dendritic Cell–Mediated Th17 Cell Response in Sjögren's Dry Eye Disease by Regulating the Acod1/STAT3 Pathway

• DOI: 10.1167/iovs.66.1.35
• Publication Date: 2025-01-14T15:54:52Z
• Authors: Yankai Wei; Mei Sun; Xinyu Zhang; Chengyuan Zhang; Chao Yang; Hong Nian; Bei Du; Ruihua Wei
• Keywords: Proinflammatory cytokine

Purpose: To investigate the role of S100A8/A9 in pathogenesis Sjögren's dry eye disease (SjDED) and explore its potential mechanism action. Methods: expression was determined by western blot quantitative real-time polymerase chain reaction (qRT-PCR). Tear secretion, corneal fluorescein staining, hematoxylin eosin staining were used to evaluate effect paquinimod, a inhibitor, on nonobese diabetic (NOD) mice. Immune cell infiltration percentage assessed immunofluorescence flow cytometry. Proinflammatory cytokine levels examined qRT-PCR or ELISA. The action analyzed using blot, immunofluorescence, chromatin immunoprecipitation. Results: upregulated peripheral blood mononuclear cells patients with SjDED lacrimal glands (LGs) upregulation correlated severity inflammatory LGs. Administration paquinimod ameliorated clinical histopathological phenotypes mice reduced proportion Th17 LGs, lymph nodes, spleens. Further experiments revealed that did not directly affect generation function but major histocompatibility complex Ⅱ (MHC Ⅱ) Th17-polarizing cytokines dendritic (DCs) augment response. Mechanistically, induced Acod1 thereby promoted activation nuclear translocation signal transducer activator transcription 3 (STAT3), resulting increased Il23a transcription. STAT3 reversed therapeutic Conclusions: activated Acod1/STAT3 pathway promote DC-driven responses SjDED. S100A8/A9/Acod1/STAT3 may represent promising target for