The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, United Kingdom.
Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, Queensland 4102, Australia.
J Immunol. 2019 Feb 15;202(4):1186-1199. doi: 10.4049/jimmunol.1800504. Epub 2019 Jan 9.
The phosphatidylserine receptor TIM4, encoded by , mediates the phagocytic uptake of apoptotic cells. We applied anti-chicken TIM4 mAbs in combination with reporter transgenes to dissect the function of TIM4 in the chick (). During development in ovo, TIM4 was present on the large majority of macrophages, but expression became more heterogeneous posthatch. Blood monocytes expressed KUL01, class II MHC, and mApple uniformly. Around 50% of monocytes were positive for surface TIM4. They also expressed many other monocyte-specific transcripts at a higher level than TIM4 monocytes. In liver, highly phagocytic TIM4 cells shared many transcripts with mammalian Kupffer cells and were associated with uptake of apoptotic cells. Although they expressed mRNA, Kupffer cells did not express the -mApple transgene, suggesting that additional transcriptional regulatory elements are required by these cells. By contrast, -mApple was detected in liver TIM4 and TIM4 cells, which were not phagocytic and were more abundant than Kupffer cells. These cells expressed alongside high levels of , , , and other markers associated with conventional dendritic cells in mice. In bursa, TIM4 was present on the cell surface of two populations. Like Kupffer cells, bursal TIM4 phagocytes coexpressed many receptors involved in apoptotic cell recognition. TIM4 cells appear to be a subpopulation of bursal B cells. In overview, TIM4 is associated with phagocytes that eliminate apoptotic cells in the chick. In the liver, TIM4 and reporters distinguished Kupffer cells from an abundant population of dendritic cell-like cells.
磷脂酰丝氨酸受体 TIM4 由 编码，介导凋亡细胞的吞噬作用。我们应用抗鸡 TIM4 mAb 与 报告基因转染结合，在鸡（）中解析 TIM4 的功能。在胚胎发育过程中，TIM4 存在于绝大多数巨噬细胞上，但孵化后表达变得更加异质。血液单核细胞均匀表达 KUL01、II 类 MHC 和 mApple。大约 50%的单核细胞呈 TIM4 阳性。它们还表达许多其他单核细胞特异性转录本，其水平高于 TIM4 单核细胞。在肝脏中，高吞噬 TIM4 细胞与哺乳动物枯否细胞共享许多转录本，并与凋亡细胞的摄取有关。尽管它们表达 mRNA，但枯否细胞不表达 -mApple 转基因，这表明这些细胞需要额外的 转录调控元件。相比之下，在肝脏 TIM4 和 TIM4 细胞中检测到 -mApple，这些细胞不具有吞噬作用，而且比枯否细胞更为丰富。这些细胞表达 以及高水平的 、 、 和其他与小鼠常规树突状细胞相关的标记物。在法氏囊中，TIM4 存在于两个细胞群体的细胞表面。与枯否细胞一样，法氏囊 TIM4 吞噬细胞共表达许多参与凋亡细胞识别的受体。TIM4 细胞似乎是法氏囊 B 细胞的一个亚群。总的来说，TIM4 与清除鸡体内凋亡细胞的吞噬细胞有关。在肝脏中，TIM4 和 报告基因区分了枯否细胞和丰富的树突状细胞样细胞群体。
