Title:Immune Mechanisms and Related Targets for the Treatment of Fibrosis in Various Organs
Volume: 22
Issue: 3
Author(s): Anita A. Pinar*Chrishan S. Samuel*
Affiliation:
- Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of
Pharmacology, Monash University, Clayton, Victoria 3800, Australia
- Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of
Pharmacology, Monash University, Clayton, Victoria 3800, Australia
Keywords:
Immune mechanisms, inflammasomes, NLRP3 inflammasome, myofibroblast differentiation, collagen deposition, fibrosis.
Abstract: 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.
