Macrophages inhibit and enhance endometriosis depending on their origin

Macrophages are intimately involved in the pathophysiology of endometriosis, a chronic inflammatory disorder characterized by the growth of endometrial-like tissue (lesions) outside the uterus. By combining genetic and pharmacological monocyte and macrophage depletion strategies we determined the ontogeny and function of macrophages in a mouse model of induced endometriosis. We demonstrate that lesion-resident macrophages are derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages (LpM) and monocytes. Furthermore, we found endometriosis to trigger continuous recruitment of monocytes and expansion of CCR2+ LpM. Depletion of eutopic endometrial macrophages results in smaller endometriosis lesions, whereas constitutive inhibition of monocyte recruitment significantly reduces peritoneal macrophage populations and increases the number of lesions. Reprogramming the ontogeny of peritoneal macrophages such that embryo-derived LpM are replaced by monocyte-derived LpM decreases the number of lesions that develop. We propose a putative model whereby endometrial macrophages are proendometriosis while newly recruited monocyte-derived macrophages, possibly in LpM form, are antiendometriosis. These observations highlight the importance of monocyte-derived macrophages in limiting disease progression.

Automated summary

Macrophages play an important role in the pathophysiology of endometriosis, with lesion-resident macrophages derived from eutopic endometrial tissue, infiltrating large peritoneal macrophages, and monocytes. Continuous recruitment of monocytes and expansion of CCR2+ large peritoneal macrophages are triggered by endometriosis. Depletion of eutopic endometrial macrophages results in smaller lesions, while inhibiting monocyte recruitment reduces macrophage populations and increases lesion number. Reprogramming the ontogeny of peritoneal macrophages decreases lesion development. The study suggests a model where endometrial macrophages promote endometriosis while newly recruited monocyte-derived macrophages, possibly in large peritoneal macrophage form, have antiendometriotic effects.