Department of Physiology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Curr Opin Hematol. 2018 May;25(3):196-203. doi: 10.1097/MOH.0000000000000421.
Macrophages are generally believed to originate entirely from the bone marrow; however, this paradigm is challenged by the discovery of yolk-sac-derived resident macrophages. Here, we provide an overview of recent advances in the ontogeny and function of resident macrophages.
Macrophage precursors from three distinct embryonic sources (yolk sac, fetal liver and bone marrow) are found to colonize various tissues via the blood circulation early during embryogenesis until shortly after birth. They differentiate into distinct long-lived resident macrophages in response to the expression of tissue-specific transcription factors. Resident macrophages are proficient at taking up tissue-specific cellular debris and consequently acquire tissue-specific imprints. They are primarily involved in homeostasis but can also support the functionality of various tissues. Under pathological settings, dysregulation of resident macrophages can promote disease progression.
Resident macrophages maintain themselves via in-situ proliferation under steady state. Following injury, bone marrow monocytes can contribute to the resident macrophage pool in adult animal. Embryonically and postnatally derived resident macrophages are similar but not identical: the former are more efficient at efferocytosis, whereas the latter are more competent at host defense. Thus, specific targeting of these two different resident macrophage populations may lead to better therapeutic strategies.
巨噬细胞通常被认为完全来源于骨髓;然而,这种观点受到了卵黄囊来源的固有巨噬细胞的发现的挑战。在这里,我们提供了固有巨噬细胞的发生和功能的最新进展概述。
在胚胎发生早期到出生后不久,通过血液循环,发现在三个不同的胚胎来源(卵黄囊、胎儿肝脏和骨髓)中有巨噬细胞前体定植于各种组织中。它们在组织特异性转录因子的表达下分化为不同的、长寿命的固有巨噬细胞。固有巨噬细胞擅长摄取组织特异性细胞碎片,并因此获得组织特异性印记。它们主要参与维持体内平衡,但也可以支持各种组织的功能。在病理状态下,固有巨噬细胞的失调可促进疾病的进展。
在稳态下,固有巨噬细胞通过原位增殖来维持自身。在损伤后,骨髓单核细胞可以为成年动物的固有巨噬细胞池做出贡献。胚胎期和出生后获得的固有巨噬细胞相似但不完全相同:前者在吞噬作用方面效率更高,而后者在宿主防御方面更有能力。因此,针对这两种不同的固有巨噬细胞群的特定靶向可能会导致更好的治疗策略。