Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Edinburgh, United Kingdom.
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
Front Endocrinol (Lausanne). 2020 Jan 23;11:7. doi: 10.3389/fendo.2020.00007. eCollection 2020.
Endometriosis is a complex, heterogeneous, chronic inflammatory condition impacting ~176 million women worldwide. It is associated with chronic pelvic pain, infertility, and fatigue, and has a substantial impact on health-related quality of life. Endometriosis is defined by the growth of endometrial-like tissue outside the uterus, typically on the lining of the pelvic cavity and ovaries (known as "lesions"). Macrophages are complex cells at the center of this enigmatic condition; they are critical for the growth, development, vascularization, and innervation of lesions as well as generation of pain symptoms. In health, tissue-resident macrophages are seeded during early embryonic life are vital for development and homeostasis of tissues. In the adult, under inflammatory challenge, monocytes are recruited from the blood and differentiate into macrophages in tissues where they fulfill functions, such as fighting infection and repairing wounds. The interplay between tissue-resident and recruited macrophages is now at the forefront of macrophage research due to their differential roles in inflammatory disorders. In some cancers, tumor-associated macrophages (TAMs) are comprised of tissue-resident macrophages and recruited inflammatory monocytes that differentiate into macrophages within the tumor. These macrophages of different origins play differential roles in disease progression. Herein, we review the complexities of macrophage dynamics in health and disease and explore the paradigm that under disease-modified conditions, macrophages that normally maintain homeostasis become modified such that they promote disease. We also interrogate the evidence to support the existence of multiple phenotypic populations and origins of macrophages in endometriosis and how this could be exploited for therapy.
子宫内膜异位症是一种复杂的、异质的、慢性炎症性疾病，影响着全球约 1.76 亿女性。它与慢性盆腔疼痛、不孕和疲劳有关，并对健康相关的生活质量有重大影响。子宫内膜异位症的定义是子宫内膜样组织在子宫外生长，通常在盆腔和卵巢的内膜上（称为“病变”）。巨噬细胞是这种神秘疾病的核心复杂细胞；它们对病变的生长、发育、血管生成和神经支配以及疼痛症状的产生至关重要。在健康状态下，组织驻留巨噬细胞在胚胎早期定植，对于组织的发育和稳态至关重要。在成人中，在炎症挑战下，单核细胞从血液中招募，并在组织中分化为巨噬细胞，在那里它们发挥功能，如抵抗感染和修复伤口。由于其在炎症性疾病中的不同作用，组织驻留巨噬细胞和募集的巨噬细胞之间的相互作用现在处于巨噬细胞研究的前沿。在一些癌症中，肿瘤相关巨噬细胞（TAMs）由组织驻留巨噬细胞和募集的炎症单核细胞组成，这些单核细胞在肿瘤内分化为巨噬细胞。这些不同来源的巨噬细胞在疾病进展中发挥不同的作用。在此，我们回顾了巨噬细胞在健康和疾病中的动态复杂性，并探讨了这样一种观点，即在疾病改变的条件下，正常维持内稳态的巨噬细胞会发生改变，从而促进疾病的发生。我们还探讨了支持在子宫内膜异位症中存在多种表型群体和巨噬细胞起源的证据，以及如何利用这一点进行治疗。
