Thymic stromal lymphopoietin contributes to endometriotic lesion proliferation and disease-associated inflammation.

Abstract

Endometriosis is a chronic disorder in which endometrial-like tissue presents outside the uterus. Patients with endometriosis have been shown to exhibit aberrant immune responses within the lesion microenvironment and in circulation which contribute to the development of endometriosis. Thymic stromal lymphopoietin (TSLP) is an alarmin involved in cell proliferation and the induction of Th2 inflammation in various diseases, such as asthma, atopic dermatitis, pancreatic and breast cancer. Recent studies have detected TSLP within endometriotic lesions and shown that its concentrations are elevated in the peritoneal fluid of patients compared to controls. However, its role in disease pathophysiology remains unclear. Here, we compared TSLP expression in endometriotic lesions to matched patient endometrium and control endometrium samples. We also assessed its effect on the proliferation and apoptosis of human endometriosis-representative cell lines, as well as on lesion development and inflammation in a mouse model of the disease. We demonstrated that TSLP expression was elevated in the stroma of patient endometriotic lesions compared to control endometrial samples. In cell lines, TSLP treatment reduced the apoptosis of endometrial stromal cells and promoted the proliferation of THP-I cells. In mice induced with endometriosis, TSLP treatment induced a Th2 immune response within the lesion microenvironment, and led to TSLP receptor modulation in macrophages, dendritic cells, and CD4+ T cells. Furthermore, treatment increased murine endometriotic lesion proliferation. Overall, these results suggest that TSLP modulates the endometriotic lesion microenvironment and promotes a Th2 immune response that could support lesion development. KEY POINTSO_LITSLP is overexpressed in the stroma of human endometriotic lesions; C_LIO_LITSLP promotes the survival of human endometrial stromal and THP-I cell lines; C_LIO_LITSLP induces Th2 inflammation and lesion proliferation. C_LI