INNATE IMMUNITY A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion

被引：417

作者：

Birchenough, George M. H. ^{[1
]}

Nystrom, Elisabeth E. L. ^{[1
]}

Johansson, Malin E. V. ^{[1
]}

Hansson, Gunnar C. ^{[1
]}

机构：

[1] Univ Gothenburg, Dept Med Biochem, S-40530 Gothenburg, Sweden

来源：

SCIENCE | 2016年 / 352卷 / 6293期

基金：

瑞典研究理事会;

关键词：

ACTIVATION;

D O I：

10.1126/science.aaf7419

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 luminalmicrobiota 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 ofMuc2 mucin fromthe 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.

引用

页码：1535 / 1542

页数：8

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