哨兵杯状细胞通过触发依赖于 Nlrp6 的 Muc2 分泌来保护结肠隐窝。
A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion.
机构信息
Department of Medical Biochemistry, University of Gothenburg, 40530 Gothenburg, Sweden.
出版信息
Science. 2016 Jun 24;352(6293):1535-42. doi: 10.1126/science.aaf7419.
Abstract
Innate immune signaling pathways contribute to the protection of host tissue when bacterially challenged. Colonic goblet cells are responsible for generating the two mucus layers that physically separate the luminal microbiota from the host epithelium. Analysis of colonic tissues from multiple mouse strains allowed us to identify a "sentinel" goblet cell (senGC) localized to the colonic crypt entrance. This cell nonspecifically endocytoses and reacts to the TLR2/1, TLR4, and TLR5 ligands by activating the Nlrp6 inflammasome downstream of TLR- and MyD88-dependent Nox/Duox reactive oxygen species synthesis. This triggers calcium ion-dependent compound exocytosis of Muc2 mucin from the senGC and generates an intercellular gap junction signal; in turn, this signal induces Muc2 secretion from adjacent goblet cells in the upper crypt, which expels bacteria. Thus, senGCs guard and protect the colonic crypt from bacterial intruders that have penetrated the inner mucus layer.
摘要
先天免疫信号通路有助于在受到细菌挑战时保护宿主组织。结肠杯状细胞负责生成两层黏液，将腔道微生物群与宿主上皮细胞物理分隔开。对来自多种小鼠品系的结肠组织进行分析，使我们能够鉴定出位于结肠隐窝入口处的“哨兵”杯状细胞（senGC）。该细胞非特异性地内吞作用，并通过激活 TLR-和 MyD88 依赖性 Nox/ Duox 活性氧合成下游的 Nlrp6 炎性小体，对 TLR2/1、TLR4 和 TLR5 配体作出反应。这会触发钙依赖性 Muc2 粘蛋白从 senGC 的化合物胞吐作用，并产生细胞间缝隙连接信号；反过来，该信号诱导上隐窝中相邻杯状细胞分泌 Muc2，从而将细菌排出。因此，senGC 可以保护结肠隐窝免受已经穿透内层黏液层的细菌入侵。
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