Immune Mechanisms and Related Targets for the Treatment of Fibrosis in Various Organs

Inflammation and fibrosis are two interrelated disease pathologies with several overlapping components. Three specific cell types, namely macrophages, T helper cells, and myofibroblasts, play important roles in regulating both processes. Following tissue injury, an inflammatory stimulus is often nec...

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Bibliographic Details
Published inCurrent molecular medicine Vol. 22; no. 3; p. 240
Main Authors Pinar, Anita A, Samuel, Chrishan S
Format Journal Article
LanguageEnglish
Published Netherlands 01.01.2022
Subjects
Cytokines - metabolism
Fibrosis
Humans
Inflammasomes - metabolism
Macrophages - metabolism
Myofibroblasts - metabolism
Myofibroblasts - pathology
collagen deposition
Immune mechanisms
fibrosis
myofibroblast differentiation
NLRP3 inflammasome
inflammasomes
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Summary:Inflammation and fibrosis are two interrelated disease pathologies with several overlapping components. Three specific cell types, namely macrophages, T helper cells, and myofibroblasts, play important roles in regulating both processes. Following tissue injury, an inflammatory stimulus is often necessary to initiate tissue repair, where cytokines released from infiltrating and resident immune and inflammatory cells stimulate the proliferation and activation of extracellular matrix-producing myofibroblasts. However, persistent tissue injury drives an inappropriate pro-fibrotic response. Additionally, activated myofibroblasts can take on the role of traditional antigen-presenting cells, secrete pro-inflammatory cytokines, and recruit inflammatory cells to fibrotic foci, amplifying the fibrotic response in a vicious cycle. Moreover, inflammatory cells have been shown to play contradictory roles in the initiation, amplification, and resolution of fibrotic disease processes. The central role of the inflammasome molecular platform in contributing to fibrosis is only beginning to be fully appreciated. In this review, we discuss the immune mechanisms that can lead to fibrosis, the inflammasomes that have been implicated in the fibrotic process in the context of the immune response to injury, and also discuss current and emerging therapies that target inflammasome-induced collagen deposition to treat organ fibrosis.
ISSN:1875-5666
DOI:10.2174/1566524022666220114122839