Solute carrier proteins in efferocytosis and inflammation

摘要：EFERO细胞增多症与炎症中的溶质载体蛋白： 我们的身体在生命中平均每秒钟翻转约一百万个细胞，这真的很了不起。这些细胞 主要是通过细胞凋亡的过程，包括作为正常细胞一部分产生的过剩细胞 疾病或感染引起的发育、使用/老化的细胞和受损的细胞。有效地去除这种 凋亡细胞对于为活细胞的替代、预防炎症、维持 组织/器官的功能，进而是一个健康的有机体。死亡细胞的有效去除是通过 吞噬过程，由专业吞噬细胞(如巨噬细胞和未成熟的树突状细胞)完成 细胞)或邻近细胞(如成纤维细胞、上皮细胞)。与配体有关的Effercytosis 对凋亡细胞和吞噬细胞上的特异性受体，具有非常有效的、积极的抗炎作用。然而， 凋亡细胞的清除障碍会导致死亡细胞的聚集，从而导致慢性炎症。 与许多病理情况有关，如动脉粥样硬化、肺部炎症和肠炎 疾病。虽然在了解凋亡细胞识别和泡细胞摄取方面取得了重大进展 近年来，仍然存在明显的差距。 溶质载体(SLC)蛋白是选择性地传导离子、代谢物和氨基酸的膜蛋白。 穿过质膜，以及特定的内部细胞膜。在人类基因组中，SLC代表 第二大家庭(仅次于GPCR)，拥有约400名SLC家庭成员。尽管有大约100种人类疾病被联系在一起 对于SLC基因的突变，SLC家族相对不了解，包括免疫系统中的7，8。 部分原因是由于SLC的功能特征通常是孤立的，没有多少SLC被作为 是一个更大的生物过程的一部分。最近，在研究吞噬细胞吞噬凋亡细胞时，我们出乎意料地 遇到了对SLC基因家族的30个成员的协调调节(Morioka等人，《自然》2018年；Perry等人， 自然细胞生物，2019年)。这一建议验证了SLC蛋白可以在不同阶段发挥关键作用的假设 胞吐作用，且在胞吐作用期间连续使用特定的SLC促进了 吞噬细胞有助于维持组织内的抗炎状态。

Abstract: SOLUTE CARRIER (SLC) PROTEINS IN EFFEROCYTOSIS AND INFLAMMATION: It is truly remarkable that our bodies turn over on average about one million cells every second of life. The cells that are turned over, predominantly by the process of apoptosis, include excess cells generated as part of normal development, used/aged cells, and damaged cells arising from disease or infections. The efficient removal of such apoptotic cells is important for ‘making space’ for replacement by living cells, preventing inflammation, maintaining the function of the tissue/organ, and in turn, a healthy organism. The efficient removal of the dying cells occurs via the process of ‘efferocytosis’, and is done by professional phagocytes (such as macrophages and immature dendritic cells) or neighboring cells (e.g. fibroblasts, epithelial cells) within a given tissue. Efferocytosis, which involves ligands on apoptotic cells and specific receptors on phagocytes, is very efficient, and actively anti-inflammatory. However, impaired clearance of apoptotic cells results in the accumulation of dead cells, and the resulting chronic inflammation linked to a number of pathological conditions such as atherosclerosis, lung inflammation, and inflammatory bowel diseases. While significant progress has been made in understanding apoptotic cell recognition and efferocytic uptake in recent years, significant gaps remain. Solute carrier (SLC) proteins are membrane proteins that selectively conduct ions, metabolites, and aminoacids across the plasma membrane, and specific internal cellular membranes. In the human genome, SLCs represent the second largest family (after the GPCRs), with ~400 SLC family members. Despite ~100 human diseases being linked to mutations in SLC genes, the SLC family is relatively understided, including in the immune system 7,8. This may in part be because the SLCs functionally characterized have often been in isolation, and not many SLCs are studied as part of a larger biological process. Recently, while studying phagocytes taking up apoptotic cells, we unexpectedly came across a coordinated regulation of >30 members of the Slc gene family (Morioka et al., Nature 2018; Perry et al, Nature Cell Biol., 2019). This proposal tests the hypothesis that SLC proteins can play key roles in different phases of efferocytosis, and that sequential use of specific SLCs during efferocytosis facilitates communication between phagocytes contributes to maintaining an anti-inflammatory state within tissues.