Abstract
Immune-mediated cholangiopathies are characterised by the destruction of small and large bile ducts causing bile acid stasis, which leads to subsequent inflammation, fibrosis, and eventual cirrhosis of the liver tissue. A breakdown of peripheral hepatic immune tolerance is a key feature of these diseases. Regulatory T cells (Tregs) are a major anti-inflammatory immune cell subset, and their quantities and functional capacity are impaired in autoimmune liver diseases. Tregs can undergo phenotypic reprogramming towards pro-inflammatory Th1 and Th17 profiles. The inflamed hepatic microenvironment influences and can impede normal Treg suppressive functions. Mast cell (MC) infiltration increases during liver inflammation, and active MCs have been shown to be an important source of pro-inflammatory mediators, thus driving pathogenesis. By influencing the microenvironment, MCs can indirectly manipulate Treg functions and inhibit their suppressive and proliferative activity. In addition, direct cell-to-cell interactions have been identified between MCs and Tregs. It is critical to consider the effects of MCs on the inflammatory milieu of the liver and their influence on Treg functions. This review will focus on the roles and crosstalk of Tregs and MCs during autoimmune cholangiopathy pathogenesis progression.
Original language | English |
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Article number | 5872 |
Journal | International Journal of Molecular Sciences |
Volume | 23 |
Issue number | 11 |
DOIs | |
Publication status | Published - 24 May 2022 |
Bibliographical note
Funding Information:Funding: N.M.K. is funded by the TransBioLine Innovative Medicine Initiative Programme. R.F. receives funding from MediMab Biotherapeutics. Y.H.O. receives funding from the Sir Jules Thorn Charity Biomedical Research Award. All authors are team members of NIHR Birmingham BRC.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords
- Fibrosis
- Humans
- Inflammation/pathology
- Liver/pathology
- Mast Cells
- T-Lymphocytes, Regulatory
- Th17 Cells
- immune tolerance
- inflammation
- plasticity
- primary biliary cholangitis
- primary sclerosing cholangitis
ASJC Scopus subject areas
- Molecular Biology
- Spectroscopy
- Catalysis
- Inorganic Chemistry
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry