Mucosal immunity in primary sclerosing cholangitis: from the bowel to bile ducts and back again
Liaskou, Evaggelia Quraishi, Mohammed Nabil Trivedi, Palak J
Liaskou, Evaggelia
Quraishi, Mohammed Nabil
Trivedi, Palak J
Abstract
Purpose of review: In this article, we provide a contemporary overview on PSC pathogenesis, with a specific focus on the role of mucosal immunity.
Recent findings: The extent of enteric dysbiosis in PSC has been extensively quantified, with evidence of reduced bacterial diversity and enrichment of species capable of driving lymphocyte recruitment from the gut to the liver. Integrative pathway-based analysis and metagenomic sequencing indicate a reduction in butyrate-producing species, near absence of bacteria that activate the nuclear bile acid receptor FXR, and depletion of species that regulate the synthesis of vitamin B6 and branched-chain amino acids. Immunotyping of the cellular inflammatory infiltrate has identified a population of intrahepatic naive T cells, with tendency to acquire a Th17 polarisation state, paralleled by heightened responses to pathogen stimulation. Moreover, the search for antigen specificity has revealed the presence of overlapping nucleotide clonotypes across the gut and liver, highlighting the ability to recognize a common pool of epitopes bearing structural similarities across afflicted sites.
Summary: Understanding the complex mechanisms that underpin mucosal immune responses between the liver and gut will help identify new druggable targets in PSC, centring on gut microbial manipulation, bile acid therapies, and restoration of immune homeostasis.
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Date
2022-03-01
Type
Article
Subject
Microbiology. Immunology
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Citation
Liaskou E, Quraishi MN, Trivedi PJ. Mucosal immunity in primary sclerosing cholangitis: from the bowel to bile ducts and back again. Curr Opin Gastroenterol. 2022 Mar 1;38(2):104-113. doi: 10.1097/MOG.0000000000000809
Journal / Source Title
Current Opinion in Gastroenterology
DOI
10.1097/MOG.0000000000000809
PMID
35034083
Publisher
Lippincott Williams & Wilkins