美国明尼苏达大学Jesse W. Williams等研究人员发现，主动脉内膜常驻巨噬细胞的增殖能力有限，需要单核细胞招募才能使动脉粥样硬化斑块进展。该研究于2020年9月7日在线发表于《自然—免疫学》。

使用鼠类谱系追踪模型和基因表达谱，研究人员发现存在于主动脉弓内膜的髓样细胞不是树突状细胞，而是依赖于集落刺激因子1并由局部增殖所维持的专门主动脉内膜常驻巨噬细胞（Mac^AIR）。尽管Mac^AIR在斑块中包含最早的泡沫细胞，但它们在斑块进展过程中的增殖受到限制。高胆固醇血症数月后，它们在斑块中的存在被招募的单核细胞所取代，后者诱导了Mac^AIR基因。

这些数据重新定义了内膜吞噬细胞的谱系，并表明增殖不足以在斑块进展期间维持巨噬细胞的产生。

据悉，早期动脉粥样硬化取决于内膜主动脉壁中驻留免疫细胞的反应。具体来说，健康的内膜被认为是由血管树突状细胞组成的，在高胆固醇血症期间，血管树突状细胞首先积累胆固醇，从而引发动脉粥样硬化。这些细胞是否仍是疾病晚期的关键因素尚不清楚。

附：英文原文

Title: Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression

Author: Jesse W. Williams, Konstantin Zaitsev, Ki-Wook Kim, Stoyan Ivanov, Brian T. Saunders, Patricia R. Schrank, Kyeongdae Kim, Andrew Elvington, Seung Hyeon Kim, Christopher G. Tucker, Mary Wohltmann, Brian T. Fife, Slava Epelman, Maxim N. Artyomov, Kory J. Lavine, Bernd H. Zinselmeyer, Jae-Hoon Choi, Gwendalyn J. Randolph

Issue&Volume: 2020-09-07

Abstract: Early atherosclerosis depends upon responses by immune cells resident in the intimal aortic wall. Specifically, the healthy intima is thought to be populated by vascular dendritic cells (DCs) that, during hypercholesterolemia, initiate atherosclerosis by being the first to accumulate cholesterol. Whether these cells remain key players in later stages of disease is unknown. Using murine lineage-tracing models and gene expression profiling, we reveal that myeloid cells present in the intima of the aortic arch are not DCs but instead specialized aortic intima resident macrophages (MacAIR) that depend upon colony-stimulating factor 1 and are sustained by local proliferation. Although MacAIR comprise the earliest foam cells in plaques, their proliferation during plaque progression is limited. After months of hypercholesterolemia, their presence in plaques is overtaken by recruited monocytes, which induce MacAIR-defining genes. These data redefine the lineage of intimal phagocytes and suggest that proliferation is insufficient to sustain generations of macrophages during plaque progression. Williams and colleagues investigate the origin, dynamics and transcriptional profiles of aortic intima macrophages during atherosclerosis disease progression.

DOI: 10.1038/s41590-020-0768-4

Source: https://www.nature.com/articles/s41590-020-0768-4