Division of Pediatric Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
Cell Mol Life Sci. 2011 Nov;68(22):3623-34. doi: 10.1007/s00018-011-0821-4. Epub 2011 Oct 11.
The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte loss by apoptosis and the generation of new cells by proliferation from stem cell precursors at the base of the intestinal crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15, in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing enterocolitis, Crohn's disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis in gastrointestinal disease.
肠道黏膜屏障平衡的维持需要肠上皮细胞凋亡和由隐窝底部干细胞前体增殖产生新细胞之间的精细和动态平衡。当这种平衡向凋亡过度或不足的方向倾斜时，广泛的胃肠道疾病就会显现出来。来自不同实验室的最新研究工作为固有免疫系统受体（包括 Toll 样受体 2、4 和 9 以及细胞内病原体识别受体 NOD2/CARD15）在肠上皮细胞凋亡的起始中的作用提供了证据。这些固有免疫受体的激活随后诱导肠上皮细胞凋亡，在各种肠道疾病（包括坏死性小肠结肠炎、克罗恩病、溃疡性结肠炎和肠癌）的发展中起着关键作用。这篇综述将详细描述调控肠上皮细胞凋亡的调控途径，并探讨固有免疫系统在诱导胃肠道疾病中肠上皮细胞凋亡中的作用。
