Abstract
BackgroundCSF-1 was found to be accumulated in the lesions and peritoneal fluid of endometriosis patients, and CSF-1 induced THP-1-derived macrophages to polarize toward a suppressive phenotype. Researchers found that macrophages were the predominant cells in the peritoneal fluid (PF) of endometriosis patients, and the primary consensus is that the immune status in the PF of endometriosis patients exhibits a depressed state. Does the cytokine CSF-1 induce monocytes to differentiate into macrophages with a DC-SIGN+ suppressive phenotype in endometriosis?MethodsThe level of CSF-1 in control endometrium (N=11), eutopic endometrium (N=17), and ectopic (N=39) endometrium of endometriosis patients was evaluated by real-time polymerase chain reaction and in the PF of control (N=25) and endometriosis (N=35) patients by enzyme-linked immunosorbent assay. CSF-1 was examined by a MILLIPLEX MAP Mouse Cytokine/Chemokine Magnetic Bead Panel in an in vivo study. DC-SIGN+ suppressive macrophages were detected by immunohistochemical staining of tissues and flow cytometric analysis of the PF of control (N=25) and endometriosis (N=35) patients. The phenotypes and biological activities of the resulting macrophages derived from THP-1 cells induced by CSF-1 were compared by an in vitro coculture system with peripheral blood lymphocytes from normal subjects.Results In this study, we found the proportion of DC-SIGN+ suppressive macrophages was larger in the abdominal immune microenvironment of endometriosis patients. CSF-1 was primarily secreted from the ectopic lesions and peritoneum of mice with endometriosis. And, CSF-1 induced the polarization of macrophages toward a DC-SIGN+ suppressive phenotype; this effect was abolished by the addition of anti-CSF-1R. CSF-1 induced DC-SIGN+ macrophages, leading to a depressed status of peripheral blood lymphocytes, including a high percentage of Treg cells and a low percentage of CD8+ T cells. Similarly, blockade with anti-CSF-1R abrogated this biological effect. This is the first study on the predominant role of DC-SIGN+ suppressive macrophages in the depressed immune status of endometriosis patients.Conclusions This is the first study on the predominant role of DC-SIGN+ suppressive macrophages in the depressed immune status of endometriosis patients. Further study of the mechanism and biological activities of CSF-1-induced DC-SIGN+ suppressive macrophages will enhance our understanding of the physiology of endometriosis and indicate new directions for further study.
Viral persistence: immunologic and molecular-genetic aspects of pathogenesis
