The expression of OX40 in CD4+ T cells and its association with hepatic fibrosis injury.

PURPOSE: OX40 is a typical member of the co-stimulatory molecule family. The signals generated by its binding to OX40L have a synergistic effect, regulating T cell proliferation, differentiation, and influencing cytokine secretion. This study aimed to evaluate the role of OX40 in regulating the progression of liver fibrosis induced by CCL4-induced inflammation.

PATIENTS AND

METHODS

OX40 expression levels in tissue samples from individuals with liver fibrosis and healthy controls were analyzed using the Gene Expression Omnibus (GEO) database. Furthermore, a murine model of liver fibrosis was established by administering CCL4 through continuous intraperitoneal injections over an 8-week period. The extent of liver fibrosis was evaluated through histopathological staining. Flow cytometry was employed to identify CD4+ T lymphocytes and to track the dynamic expression of OX40 on these cells in splenic samples throughout the progression of liver fibrosis.

RESULTS

Database analysis revealed that OX40 expression was significantly upregulated in liver fibrosis tissues compared to corresponding normal tissues. Following CCL4 induction, there was a marked increase in alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. Hematoxylin and eosin (HE) staining, along with Masson's trichrome staining, highlighted the presence of damaged tissue architecture in the murine models. Additionally, the upregulation of OX40 expression in liver fibrosis showed a positive correlation with elevated levels of alpha-smooth muscle actin (α-SMA) and the production of collagen fibers. ELISA results indicate that interference with the OX40 molecule can affect cytokine expression. Blocking the OX40-OX40L signaling pathway can, to some extent, regulate the direction of immune polarization.

CONCLUSION

These results suggest that the OX40 molecule may be involved in the immune imbalance occurring during the development and progression of liver fibrosis, thereby contributing to hepatic tissue injury.