Rediscovering peritoneal macrophages in a murine endometriosis model

Abstract

Study question: What are the features of peritoneal macrophage subgroups and T helper cells in the development of murine endometriosis?

Summary answer: During the development of endometriosis in a murine model, large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs) are polarized into M1 and M2 cells, respectively, and the proportions of T helper (Th) 1, Th17 and T regulatory (T_reg) cells are increased.

What is known already: Numerous studies investigating the etiology and pathogenesis of endometriosis have focused on the polarization states of peritoneal macrophages in endometriosis models and patients, but the results are inconclusive. Further studies indicate that peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs, although their roles in endometriosis are unknown.

Study design, size, duration: This study involves a prospective and randomized experiment. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group) according to the presence or absence of transplantation. The transplant periods are 0.25, 3, 14, 28 and 42 days.

Participants/materials, setting, methods: C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of allogeneic endometrial segments. Dynamic changes of peritoneal macrophage subsets and polarization profiles were evaluated by flow cytometry (FCM). Macrophage morphology and density were assessed by cell counting under a microscope. Dynamic changes of Th1, Th2, Th17 and T_reg cells were estimated by FCM.

Main results and the role of chance: Peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs. The proportion of SPMs increased immediately after peritoneal injection of endometrial tissues, whereas LPMs showed an opposite trend. Peritoneal macrophages differentiated into both M1 and M2 macrophages. The bidirectional polarization of macrophages was caused by the inverse trends of polarization of LPMs and SPMs. Consistently, the proportions of Th1, Th17 and T_reg cells were all increased in mice with endometriosis.

Large scale data: N/A.

Limitations, reasons for caution: In this study, detection was only performed in a murine endometriosis model. Clinical data and more intervention experiments are required in understanding the roles of LPMs and SPMs in endometriosis.

Wider implications of the findings: The dramatic changes of LPMs and SPMs in proportion and polarization profiles clarified the varying differentiation states of peritoneal macrophages. In addition, LPMs and SPMs may play different roles in the pathogenesis of endometriosis in different stages of endometriosis. Therefore, the new classification should be included in future relevant basic and clinical studies on endometriosis.

Study funding/competing interests: This research was supported totally by grant 81270671 from the National Natural Science Foundation of China. The authors report no conflict of interest.

Keywords: T helper cell; endometriosis; immunity; large peritoneal macrophages; macrophage polarization; small peritoneal macrophages.