CCL2/CCR4 participates in mast cell-mediated epithelial mesenchymal transition in endometriosis

Do mast cells play a role in the pathogenesis of endometriosis and, if so, what is the mechanism of action?

The study included 18 women with ovarian endometriosis and 13 women without endometriosis. Primary endometrial epithelial cells (EPC) were isolated and purified, and co-cultured with human mast cell line HMC-1.1 to explore the role and mechanisms of mast cells on epithelial mesenchymal transition (EMT) in EPC in vitro. Then, wild/c-kit^sh mouse model of endometriosis was established by abdominal allogeneic endometrial transplantation in vivo. The number and location of mast cells in human/mouse endometrial tissue were determined by immunofluorescence staining. The expression levels of molecules related to CCL2, CCR4 and EMT were measured by quantitative reverse transcription polymerase chain reaction, Western blot and immunohistochemical staining analysis, respectively.

The number of infiltrated activated mast cells was positively correlated with EMT in human endometriotic lesions (CDH2, r = 0.53, P = 0.002; CDH1, r = -0.72, P < 0.001). Subsequently, mast cells promoted the migration and EMT of EPC through Mas-related G-protein-coupled receptor X2 (MRGPRX2)/C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor 4 (CCR4) signalling pathway in vitro. Finally, wild/c-kit^sh mouse model of endometriosis showed that deficiency of mast cell activation suppressed the development of endometriosis via the restriction of EMT.

Mast cells are involved in the pathogenesis of endometriosis via MRGPRX2/CCL2/CCR4/EMT signals, thus providing a potential novel therapeutic approach for the treatment of endometriosis by targeting MRGPRX2/CCL2/CCR4 pathway.