Location-specific cell identity rather than exposure to GI microbiota defines many innate immune signalling cascades in the gut epithelium.

Abstract:

OBJECTIVE:The epithelial layer of the GI tract is equipped with innate immune receptors to sense invading pathogens. Dysregulation in innate immune signalling pathways is associated with severe inflammatory diseases, but the responsiveness of GI epithelial cells to bacterial stimulation remains unclear. DESIGN:We generated 42 lines of human and murine organoids from gastric and intestinal segments of both adult and fetal tissues. Genome-wide RNA-seq of the organoids provides an expression atlas of the GI epithelium. The innate immune response in epithelial cells was assessed using several functional assays in organoids and two-dimensional monolayers of cells from organoids. RESULTS:Results demonstrate extensive spatial organisation of innate immune signalling components along the cephalocaudal axis. A large part of this organisation is determined before birth and independent of exposure to commensal gut microbiota. Spatially restricted expression of Toll-like receptor 4 (Tlr4) in stomach and colon, but not in small intestine, is matched by nuclear factor kappa B (NF-κB) responses to lipopolysaccharide (LPS) exposure. Gastric epithelial organoids can sense LPS from the basal as well as from the apical side. CONCLUSION:We conclude that the epithelial innate immune barrier follows a specific pattern per GI segment. The majority of the expression patterns and the function of TLR4 is encoded in the tissue-resident stem cells and determined primarily during development.

journal_name

Gut

journal_title

Gut

authors

Kayisoglu O,Weiss F,Niklas C,Pierotti I,Pompaiah M,Wallaschek N,Germer CT,Wiegering A,Bartfeld S

doi

10.1136/gutjnl-2019-319919

subject

Has Abstract

pub_date

2020-06-22 00:00:00

eissn

0017-5749

issn

1468-3288

pii

gutjnl-2019-319919

pub_type

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