Programmed cell removal by calreticulin in tissue homeostasis and cancer
Programmed cell removal by calreticulin in tissue homeostasis and cancer
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DOI：
10.1038/s41467-018-05211-7
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发表时间：
2018-08-10
影响因子：
16.6
通讯作者：
Weissman, Irving L.
中科院分区：
文献类型：
--
作者：
Feng, Mingye;Marjon, Kristopher D.;Weissman, Irving L.
巨噬细胞介导的程序性细胞清除（PrCR）是清除不需要的（受损，功能失调，老化或有害）细胞的关键过程。通过巨噬细胞检测和识别合适的靶细胞是成功的PrCR的关键步骤，但其分子机制尚未阐明。在这里，使用组织周转，癌症免疫监视和造血干细胞的模型，我们表明，不需要的细胞，如老化的中性粒细胞和活的癌细胞容易被巨噬细胞分泌的钙网蛋白（CRT）“标记”，使其清除通过PrCR。重要的是，我们确定了CRT结合调节PrCR的靶细胞上的脱唾液酸聚糖，并且癌细胞上这种CRT结合位点的可用性与各种恶性肿瘤患者的预后相关。我们的研究揭示了巨噬细胞识别靶细胞的一般机制，这是PrCR在生理和病理生理过程中清除不需要的细胞的关键。
Macrophage-mediated programmed cell removal (PrCR) is a process essential for the clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The detection and recognition of appropriate target cells by macrophages is a critical step for successful PrCR, but its molecular mechanisms have not been delineated. Here using the models of tissue turnover, cancer immunosurveillance, and hematopoietic stem cells, we show that unwanted cells such as aging neutrophils and living cancer cells are susceptible to "labeling" by secreted calreticulin (CRT) from macrophages, enabling their clearance through PrCR. Importantly, we identified asialoglycans on the target cells to which CRT binds to regulate PrCR, and the availability of such CRT-binding sites on cancer cells correlated with the prognosis of patients in various malignancies. Our study reveals a general mechanism of target cell recognition by macrophages, which is the key for the removal of unwanted cells by PrCR in physiological and pathophysiological processes.