State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
J Proteome Res. 2024 Nov 1;23(11):5166-5176. doi: 10.1021/acs.jproteome.4c00681. Epub 2024 Oct 9.
Macrophages make up a heterogeneous population of immune cells that exhibit diverse phenotypes and functions in health and disease. Although macrophage epigenomic and transcriptomic profiles have been reported, the proteomes of distinct macrophage populations under various pathological conditions remain largely elusive. Here, we employed a label-free proteomic approach to characterize the diversity of the hepatic macrophage pool in an experimental model of CCl-induced liver fibrosis. We found a decrease in the proportion of liver resident embryo-derived KCs (EmKCs), and a drastic increase in the proportion of monocyte-derived KCs (MoKCs) and CLEC2Macs. Proteomic profiling revealed that MoKCs largely resembled EmKCs, whereas CLEC2Macs exhibited greater proteomic alternations compared with EmKCs, suggesting two distinct destinations for monocyte differentiation during liver fibrosis. Furthermore, CLEC2Macs were characterized by increased expression of proteins associated with inflammatory response, antigen processing and presentation processes, which may be involved in the pathogenesis of liver fibrosis. Collectively, our study provides insights into the considerable heterogeneity within the hepatic macrophage pool during liver fibrosis.
巨噬细胞是一类异质性的免疫细胞群体，在健康和疾病状态下表现出不同的表型和功能。尽管已经报道了巨噬细胞的表观基因组和转录组图谱，但在各种病理条件下不同巨噬细胞群体的蛋白质组仍然很大程度上难以捉摸。在这里，我们采用无标记蛋白质组学方法来描述 CCl 诱导的肝纤维化实验模型中肝巨噬细胞库的多样性。我们发现肝驻留胚胎衍生的 KC（EmKC）的比例下降，而单核细胞衍生的 KC（MoKC）和 CLEC2Mac 的比例急剧增加。蛋白质组学分析表明，MoKC 与 EmKC 非常相似，而 CLEC2Mac 与 EmKC 相比表现出更大的蛋白质组改变，这表明单核细胞在肝纤维化过程中分化为两个不同的目的地。此外，CLEC2Mac 表达的与炎症反应、抗原加工和呈递过程相关的蛋白增加，这可能与肝纤维化的发病机制有关。总之，我们的研究提供了在肝纤维化过程中肝巨噬细胞库内存在相当大的异质性的见解。
