TY - JOUR
T1 - Epithelial Toll-like receptors and their role in gut homeostasis and disease
AU - Burgueño, Juan F.
AU - Abreu, Maria T.
N1 - Funding Information:
M.T.A. is supported by grants from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099076, R01DK104844 and T32DK11678), Crohn’s and Colitis Foundation Award IBD-0389R, the Florida Academic Cancer Center Alliance (FACCA) Award, the Pfizer ASPIRE Award and the Takeda Pharmaceuticals Investigator Initiated Research (IIR) Award. Additional funding provided by The Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory and Martin Kalser Chair. The authors acknowledge J. Fritsch and J. Pignac-Kobinger for preparing the initial figures for submission.
Funding Information:
M.T.A. is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099076, R01DK104844 and T32DK11678), Crohn’s and Colitis Foundation Award IBD-0389R, the Florida Academic Cancer Center Alliance (FACCA) Award, the Pfizer ASPIRE Award and the Takeda Pharmaceuticals Investigator Initiated Research (IIR) Award. Additional funding provided by The Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory and Martin Kalser Chair. The funders had no role in the article’s conception, interpretation of data, or preparation of the manuscript. M.T.A. has served as a consultant for Boehringer Ingelheim Pharmaceuticals, Gilead, Janssen, Abbvie, Eli Lilly and Landos Biopharma; and serves as a trainer or lecturer for Imedex, Focus Medical Communications and Cornerstones Health, Inc. This does not alter the authors’ adherence to the journal’s policies on sharing data and materials. J.F.B. declares no competing interests.
Publisher Copyright:
© 2020, Springer Nature Limited.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - The human gastrointestinal tract is colonized by trillions of microorganisms that interact with the host to maintain structural and functional homeostasis. Acting as the interface between the site of the highest microbial burden in the human body and the richest immune compartment, a single layer of intestinal epithelial cells specializes in nutrient absorption, stratifies microorganisms to limit colonization of tissues and shapes the responses of the subepithelial immune cells. In this Review, we focus on the expression, regulation and functions of Toll-like receptors (TLRs) in the different intestinal epithelial lineages to analyse how epithelial recognition of bacteria participates in establishing homeostasis in the gut. In particular, we elaborate on the involvement of epithelial TLR signalling in controlling crypt dynamics, enhancing epithelial barrier integrity and promoting immune tolerance towards the gut microbiota. Furthermore, we comment on the regulatory mechanisms that fine-tune TLR-driven immune responses towards pathogens and revisit the role of TLRs in epithelial repair after injury. Finally, we discuss how dysregulation of epithelial TLRs can lead to the generation of dysbiosis, thereby increasing susceptibility to colitis and tumorigenesis.
AB - The human gastrointestinal tract is colonized by trillions of microorganisms that interact with the host to maintain structural and functional homeostasis. Acting as the interface between the site of the highest microbial burden in the human body and the richest immune compartment, a single layer of intestinal epithelial cells specializes in nutrient absorption, stratifies microorganisms to limit colonization of tissues and shapes the responses of the subepithelial immune cells. In this Review, we focus on the expression, regulation and functions of Toll-like receptors (TLRs) in the different intestinal epithelial lineages to analyse how epithelial recognition of bacteria participates in establishing homeostasis in the gut. In particular, we elaborate on the involvement of epithelial TLR signalling in controlling crypt dynamics, enhancing epithelial barrier integrity and promoting immune tolerance towards the gut microbiota. Furthermore, we comment on the regulatory mechanisms that fine-tune TLR-driven immune responses towards pathogens and revisit the role of TLRs in epithelial repair after injury. Finally, we discuss how dysregulation of epithelial TLRs can lead to the generation of dysbiosis, thereby increasing susceptibility to colitis and tumorigenesis.
UR - http://www.scopus.com/inward/record.url?scp=85080088578&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85080088578&partnerID=8YFLogxK
U2 - 10.1038/s41575-019-0261-4
DO - 10.1038/s41575-019-0261-4
M3 - Review article
C2 - 32103203
AN - SCOPUS:85080088578
VL - 17
SP - 263
EP - 278
JO - Nature Reviews Gastroenterology and Hepatology
JF - Nature Reviews Gastroenterology and Hepatology
SN - 1759-5045
IS - 5
ER -