ATG8 inhibited endometriosis formation by regulating Treg cells differentiation via integrin α4ß1 and Talin-1 interaction.

ABSTRACT

RESEARCH QUESTION What is the relationship between ATG8 and integrin α4ß1, Talin-1, and Treg cell differentiation, and the effects on endometriosis (EMS)? DESIGN: First, the correlation between the ATG8, Talin-1, integrin α4ß1, and differentiation of Treg cells and EMS was examined in clinical samples. Human peripheral blood mononuclear cells (PBMC) and endometrial stromal cells were extracted and identified, oe-ATG8 and oe-integrin α4ß1 were transfected to overexpress ATG8 and integrin α4ß1, and Tregs cell differentiation and endometrial stromal cells (ESC) function were detected. In addition, the molecular mechanism by which ATG8 inhibited EMS disease progression at the molecular and animal levels was investigated. RESULTS: ATG8 expression was negatively correlated with positive proportion of Tregs cells (P = 0.0463). The expression of Talin-1 and integrin-α4ß1 (both P < 0.0001) in PBMC decreased significantly after oe-ATG8 transfection, whereas the Treg cells' positive rate significantly increased (P = 0.0003). The ESC proliferation, adhesion, migration, and invasion (all P < 0.0001) declined after co-culture with Treg cells that underwent oe-ATG8 transfection. The expression of Talin-1 (P = 0.0025) and integrin-α4ß1 (P = 0.0002) in PBMC increased significantly after oe-integrin α4ß1 and oe-ATG8 transfection. In addition, this transfection reversed the corresponding regulation of oe-ATG8 transfection. Finally, animal experiments in vivo confirmed that ATG8 inhibited EMS disease progression. CONCLUSION: The ATG8 regulated Treg cell differentiation and inhibited EMS formation by influencing the interaction between integrin α4ß1 and Talin-1.