Yiguanjian alleviates ocular surface inflammation and lacrimal gland immune dysregulation in experimental dry eye disease: evidence from in vivo and in vitro models.

Authors

Yuan Zhong, Jian Shi, Xiyuan Liu, Yanwen Zhang, Qinghua Peng, Jun Peng

Published in

Frontiers in medicine. Volume 13. Pages 1915720. Epub Sep 28, 2026.

Abstract

Persistent ocular surface inflammation and lacrimal gland immune dysregulation are central to the progression of dry eye disease (DED). Th17/Treg imbalance contributes to sustained inflammatory activation in the ocular surface and lacrimal gland. Yiguanjian (YGJ) has anti-inflammatory and immunomodulatory potential, but whether it can alleviate ocular surface inflammation and restore lacrimal gland immune homeostasis in DED remains unclear.
A benzalkonium chloride (BAC)-induced rat DED model was used to assess the effects of YGJ on tear secretion, tear film break-up time, corneal fluorescein staining, ocular histopathology, lacrimal gland Th17/Treg proportions, related gene expression, and STAT3 signaling. Yiguanjian-containing serum (YCS) was prepared, and its serum-associated chemical features were characterized by UHPLC-Q-Orbitrap HRMS. A hyperosmotic non-contact co-culture system of rat lacrimal gland epithelial cells and activated CD4⁺ T cells was established to evaluate epithelial cell viability, intracellular reactive oxygen species (ROS), Th17/Treg differentiation, Foxp3 and IL-17A immunofluorescence signals, and related gene expression. AS2863619 and Peptide P60 were used to explore Foxp3-associated regulation.
In BAC-induced dry eye rats, YGJ improved tear secretion and tear film stability, reduced corneal fluorescein staining, and alleviated corneal and lacrimal gland histopathological injury, with partial preservation of meibomian gland and conjunctival morphology. YGJ reduced lacrimal gland Th17 proportions, restored Treg proportions, increased Foxp3 and IL-10 expression, decreased RORγt and IL-17A expression, and reduced lacrimal gland STAT3 phosphorylation. UHPLC-Q-Orbitrap HRMS yielded 67 candidate annotations corresponding to 56 distinct LC-MS features in YCS. In the hyperosmotic co-culture model, YCS improved epithelial cell viability, reduced ROS accumulation in CD4⁺ T cells, suppressed Th17-related responses, and enhanced Treg-associated immunoregulation. AS2863619 produced effects comparable to YCS, whereas Peptide P60 weakened Foxp3-associated immunoregulation; combined YCS treatment partially attenuated Peptide P60-induced changes.
YGJ attenuated DED-related inflammatory injury in vivo and modulated lacrimal gland epithelial cell-CD4⁺ T-cell inflammatory interactions in vitro. These findings were accompanied by reduced lacrimal gland STAT3 phosphorylation in vivo and lower ROS accumulation in CD4⁺ T cells in vitro, together with Foxp3-associated improvement of the Th17/Treg balance; however, the causal relationship between the STAT3 and ROS findings was not established.

PMID:
42865459
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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