Immunosuppression of Myeloid Derived Suppressor Cells During Early Development of Endometriosis

Normal immune system keeps human bodies remain intact and unharmed in the midst of a vast universe of pathogens. The immune system includes a series of cells and molecules which worked together to initiate immune response. The dysfunction of immune cells or modulators results in various diseases, such as allergic diseases, autoimmune diseases and tumors. Endometriosis is a chronic gyneacological disorder characterized by the implantation of endometrial glands and stroma outside the uterus. The successful immune escape of retrograded endometrial cell from immune surveillance is one of the key steps in the development of endometriosis. The underlying mechanism is still unknown.;In this study, we observed the profiles of peritoneal immune cells and cytokines within 24 hours (h) after the transplantation of endometrial fragments in peritoneal cavity in mice. Most of the peritoneal immune cells decreased after the transplantation, except myeloid derived suppressor cells (MDSC) were significantly increased within 24 h. MDSC was increased in the peritoneal cavity as early as 6 h and maintained at high level when the endometrial fragments attached and proliferated in the following days. The increased MDSC have CD11b +Ly-6G+Ly-6Clow granulocytic MDSC (G-MDSC) and CD11b+Ly-6G-Ly-6Chigh monocytic MDSC (M-MDSC) phenotypes. Isolated peritoneal MDSC significantly suppressed T cell proliferation and activated arginase activity, suggesting the immunosuppression of MDSC during early development of endometriosis. Depletion of MDSC by Gr-1 antibody treatment significantly reduced the growth and development of endometriosis. Concurrently, granulocyte colony stimulating factor (G-CSF) was significantly increased as early as 6 h after transplantation. Supplementation of G-CSF in control mice increased MDSC percentage in bone marrow and peripheral blood, but not in peritoneal cavity. This suggests that G-CSF is responsible to induce the proliferation of MDSC in bone marrow and accumulation of MDSC in peripheral blood, but not recruitment into peritoneal cavity. Additional cytokines or chemokines may involve the mobilization of MDSC from peripheral blood to peritoneal cavity.;Our study suggested that MDSC may play an essential role in the immune escape and promote endometrial survival during early development of endometriosis, probably through the similar immunosuppression mechanisms as in cancer. MDSC may be a novel target to develop highly effective therapeutics for treatment of endometriosis.