Back to Search
Start Over
The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2019
-
Abstract
- It is thought that the Nlrp6 inflammasome regulates formation of the inner mucus layer (IML) barrier that prohibits contact between the microbiota and colonic epithelial cells. Using microbiota-controlled mice and combined ex vivo/in vivo IML analytical approaches, Volk et al. delineate the relative roles of the inflammasome and microbiota in shaping IML formation and function.<br />The inner mucus layer (IML) is a critical barrier that protects the colonic epithelium from luminal threats and inflammatory bowel disease. Innate immune signaling is thought to regulate IML formation via goblet cell Nlrp6 inflammasome activity that controls secretion of the mucus structural component Muc2. We report that isolated colonic goblet cells express components of several inflammasomes; however, analysis of IML properties in multiple inflammasome-deficient mice, including littermate-controlled Nlrp6−/−, detect a functional IML barrier in all strains. Analysis of mice lacking inflammasome substrate cytokines identifies a defective IML in Il18−/− mice, but this phenotype is ultimately traced to a microbiota-driven, Il18-independent effect. Analysis of phenotypic transfer between IML-deficient and IML-intact mice finds that the Bacteroidales family S24-7 (Muribaculaceae) and genus Adlercrutzia consistently positively covary with IML barrier function. Together, our results demonstrate that baseline IML formation and function is independent of inflammasome activity and highlights the role of the microbiota in determining IML barrier function.
- Subjects :
- Mice, Knockout
Mucin-2
Colon
Inflammasomes
Interleukin-18
Mice, Transgenic
Receptors, Cell Surface
Inflammatory Bowel Diseases
digestive system
Article
Gastrointestinal Microbiome
Mice, Inbred C57BL
stomatognathic diseases
Mucus
fluids and secretions
Animals
Goblet Cells
Intestinal Mucosa
Research Articles
Signal Transduction
Subjects
Details
- ISSN :
- 15409538
- Volume :
- 216
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- The Journal of experimental medicine
- Accession number :
- edsair.pmid..........bbadab2200413c5056fdfd2598989f5c