Decrease in CD226 expression on CD4⁺ T cells in patients with endometriosis

Endometriosis is a chronic inflammatory disease. The immune-checkpoint molecules CD226 and TIGIT play an important role in regulating T cells' function. However, little is known about the proportion and function of CD226 and TIGIT on CD4⁺ T cells in endometriosis. The current study found no significant differences in the TIGIT percentage on peripheral CD4⁺ T cells between patients with endometriosis and the control group. However, CD226 was lower in patients with endometriosis than that in the control group (P < 0.01). The cytokines TNF-α, IL10, and IFN-γ were significantly elevated in TIGIT⁺ CD4⁺ T cells compared to TIGIT- CD4⁺ T cells. HLA-DR⁺ cells were more numerous among TIGIT⁺ CD4⁺ T cells than among the TIGIT- subset (P <0.001). Similarly, the cytokines TNF-α, IL10, and IFN-γ were significantly elevated in CD226⁺ CD4⁺ T cells compared to levels in CD226- CD4⁺ T cells. The proportion of HLA-DR⁺ CD4⁺ T cells among CD226⁺ CD4⁺ T cells was also significantly higher than that among the CD226- subset (P < 0.001). After TIGIT was blocked, the level of IL-10 in TIGIT⁺ CD4⁺ T cells was higher than that in cells with unblocked TIGIT. There were no differences in TNF-α and IFN-γ. After CD226 was blocked, TNF-α and IFN-γwere lower while IL-10 was higher. In conclusion, there is a diminution of CD226 in CD4⁺ T cells in patients with endometriosis. This is correlated with the effector function of CD4⁺ T cells, and blocking CD226 can suppress this function.