Emerging roles of renal intercalated cells

肾脏是一个复杂的器官，因为它的各种管状节段的“串联”组织。收集管穿过肾皮质（皮质收集管），然后穿过髓质（外髓质和内髓质），最后在肾盂中释放尿液。它由至少三种不同的细胞类型组成：主细胞（PC），A型和B型闰间细胞（IC）。虽然教科书目前将主细胞描述为介导钠和水重吸收，IC负责酸碱平衡，但最近的体内研究结果支持这些不同细胞类型具有更多功能。因此，我们必须重新评估每种细胞类型对正常肾脏生理学的功能。** 最近的研究表明，除了泌酸功能外，A型IC在抗尿路致病性大肠杆菌的天然免疫中也起重要作用。大肠杆菌（UPEC）。此外，外髓集合管中的A型IC可以重塑为具有侧向胞质突起的树突状细胞，支持A型IC可能在肾生理学中的酸碱平衡中发挥不止一种作用。然而，在这个时候，细胞内和细胞外机制，导致IC的功能，先天免疫的细胞重塑是未知的。** 该计划的长期目标是破译肾脏生理学中插入和主要细胞类型的多重和互补作用。我们的短期目标是剖析调节IC在正常肾脏生理学，特别是先天免疫中作用的细胞机制。该计划与我们目前资助的研究没有概念或预算重叠，是我们计划在未来十年开发的独立研究部门。利用细胞生物学和生物化学方法对骨髓IC的永生化细胞模型，我们将确定UPEC附着位点IC，并剖析由此产生的细胞内信号传导途径，激素调节和细胞重塑，导致IC介导的肾保护。该项目的结果将有助于更好地了解IC在肾脏生理学和免疫中的作用。**

The kidney is a complex organ due to the “in series” organization of its various tubular segments. The collecting duct runs through the renal cortex (cortical collecting duct) and then the medulla (outer and inner medulla) prior to releasing final urine in the renal pelvis. It is composed of at least three different cell types: principal cells (PC), type-A and type-B intercalated cells (IC). While textbooks currently describe principal cells as mediating sodium and water reabsorption, and IC as responsible for acid-base homeostasis, recent in vivo findings support more versatile functions for these various cell types. We thus have to re-evaluate the function(s) of each cell type to normal renal physiology. ******Recent studies support that in addition to their acid-secreting function, type-A IC also play an essential role in innate immunity against uropathogenic E. coli (UPEC). Further, type-A IC in the outer medullary collecting duct can remodel into dendritic-like cells with lateral cytoplasmic projections, supporting that type-A IC may play more than just one role in acid-base homeostasis in renal physiology. However, at this time the intracellular and extracellular machinery that results in the cellular remodeling of IC's function to innate immunity is unknown. ******The long-term objective of this program is to decipher the multiple and complementary roles of intercalated and principal cell types in renal physiology. Our short-term objective is to dissect the cellular mechanisms that regulate the role IC play in normal renal physiology, in particular in innate immunity. This program has no conceptual or budgetary overlap with our currently funded research and is an independent research arm that we aim to develop in the next decade. Using cell biology and biochemical approaches on immortalized cell models of medullary IC, we will identify the UPEC attachment site to IC, and dissect the resulting intracellular signalling pathway(s), the hormonal regulation and cellular remodelling that lead to IC-mediated renal protection. Results from this program will contribute to a better understanding of the role(s) of IC in renal physiology and immunity.**