Interplay between Mast Cells and Regulatory T Cells in Immune-Mediated Cholangiopathies

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.

Revisiting regulatory T cells as modulators of innate immune response and inflammatory diseases

“…Overall, therefore, the interplay between Treg and MC is clearly complex with diverse potential outcomes, necessitating further, context-dependent research before it can be directly exploited for therapeutic purposes. A recent comprehensive review focused on therapeutic opportunities for cholangiopathies provides a more detailed delineation of Treg/MC cross talk (72).…”

Mast Cell and Innate Immune Cell Communication in Cholestatic Liver Disease

“…[8] A comprehensive overview of MC contribution to the progression of liver diseases, including cholestatic disease, was recently reviewed here [14,15]. Although the interactions between MCs and innate immune cells to promote the adaptive immune response [16] and regulatory T cells during cholangiopathies [17] have been well described, there is little known about the interactions that MCs have with other innate immune cells during cholestasis. The purpose of this review is to describe previously identified MC-innate immune cell interactions, which may play a role, directly or indirectly, in cholestatic liver diseases.…”