PMID- 32571970
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20211129
IS  - 1468-3288 (Electronic)
IS  - 0017-5749 (Print)
IS  - 0017-5749 (Linking)
VI  - 70
IP  - 4
DP  - 2021 Apr
TI  - Location-specific cell identity rather than exposure to GI microbiota defines 
      many innate immune signalling cascades in the gut epithelium.
PG  - 687-697
LID - 10.1136/gutjnl-2019-319919 [doi]
AB  - 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-kappaB) 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.
CI  - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Kayisoglu, Ozge
AU  - Kayisoglu O
AD  - Research Center for Infectious Diseases (ZINF)/Institute for Molecular Infection 
      Biology (IMIB), Julius Maximilian University of Wuerzburg, Wuerzburg, Germany.
FAU - Weiss, Franziska
AU  - Weiss F
AD  - Research Center for Infectious Diseases (ZINF)/Institute for Molecular Infection 
      Biology (IMIB), Julius Maximilian University of Wuerzburg, Wuerzburg, Germany.
FAU - Niklas, Carolin
AU  - Niklas C
AD  - Research Center for Infectious Diseases (ZINF)/Institute for Molecular Infection 
      Biology (IMIB), Julius Maximilian University of Wuerzburg, Wuerzburg, Germany.
FAU - Pierotti, Isabella
AU  - Pierotti I
AD  - Research Center for Infectious Diseases (ZINF)/Institute for Molecular Infection 
      Biology (IMIB), Julius Maximilian University of Wuerzburg, Wuerzburg, Germany.
FAU - Pompaiah, Malvika
AU  - Pompaiah M
AD  - Research Center for Infectious Diseases (ZINF)/Institute for Molecular Infection 
      Biology (IMIB), Julius Maximilian University of Wuerzburg, Wuerzburg, Germany.
FAU - Wallaschek, Nina
AU  - Wallaschek N
AD  - Research Center for Infectious Diseases (ZINF)/Institute for Molecular Infection 
      Biology (IMIB), Julius Maximilian University of Wuerzburg, Wuerzburg, Germany.
FAU - Germer, Christoph-Thomas
AU  - Germer CT
AD  - Department of General, Visceral, Vascular and Pediatric Surgery, University 
      Hospital of Wuerzburg, Wuerzburg, Germany.
FAU - Wiegering, Armin
AU  - Wiegering A
AD  - Department of General, Visceral, Vascular and Pediatric Surgery, University 
      Hospital of Wuerzburg, Wuerzburg, Germany.
FAU - Bartfeld, Sina
AU  - Bartfeld S
AUID- ORCID: 0000-0003-2493-8282
AD  - Research Center for Infectious Diseases (ZINF)/Institute for Molecular Infection 
      Biology (IMIB), Julius Maximilian University of Wuerzburg, Wuerzburg, Germany 
      bartfeld@gmx.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200622
PL  - England
TA  - Gut
JT  - Gut
JID - 2985108R
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Epithelial Cells/*immunology
MH  - Gastrointestinal Microbiome/*immunology
MH  - Humans
MH  - Immunity, Innate/*physiology
MH  - Intestinal Mucosa/*cytology/*immunology
MH  - Lipopolysaccharides/immunology
MH  - Organoids/*immunology
MH  - Signal Transduction
PMC - PMC7948175
OTO - NOTNLM
OT  - epithelial barrier
OT  - gastrointestinal immune response
OT  - mucosal immunity
COIS- Competing interests: None declared.
EDAT- 2020/06/24 06:00
MHDA- 2021/11/30 06:00
PMCR- 2021/03/11
CRDT- 2020/06/24 06:00
PHST- 2019/09/21 00:00 [received]
PHST- 2020/05/06 00:00 [revised]
PHST- 2020/05/19 00:00 [accepted]
PHST- 2020/06/24 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2020/06/24 06:00 [entrez]
PHST- 2021/03/11 00:00 [pmc-release]
AID - gutjnl-2019-319919 [pii]
AID - 10.1136/gutjnl-2019-319919 [doi]
PST - ppublish
SO  - Gut. 2021 Apr;70(4):687-697. doi: 10.1136/gutjnl-2019-319919. Epub 2020 Jun 22.