Programmed Cell Death Pathways in the Pathogenesis of Idiopathic Inflammatory Myopathies.

Jia Shi,Xinping Tian,Qian Wang,Shuang Zhou,Mingwei Tang,Dong Xu,Chanyuan Wu,Mengtao Li,Jiuliang Zhao,Xiaofeng Zeng

doi:10.3389/fimmu.2021.783616

Abstract

Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of acquired, autoimmune muscle diseases characterized by muscle inflammation and extramuscular involvements. Present literatures have revealed that dysregulated cell death in combination with impaired elimination of dead cells contribute to the release of autoantigens, damage-associated molecular patterns (DAMPs) and inflammatory cytokines, and result in immune responses and tissue damages in autoimmune diseases, including IIMs. This review summarizes the roles of various forms of programmed cell death pathways in the pathogenesis of IIMs and provides evidence for potential therapeutic targets.

Highlights

Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of acquired, autoimmune muscle diseases characterized by production of a spectrum of autoantibodies [including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs)], aberrant regulation of inflammatory responses, and tissue damage of different organs
Accumulating evidences have revealed that excessive cell death in combination with impaired elimination of dead cells and debris contribute to the release of autoantigens, danger-associated molecular patterns (DAMPs) and proinflammatory cytokines, and the over-activated immune and inflammatory responses in IIMs [5]
We focus on recent research progression of programmed cell death (PCD) pathways in the pathogenesis and progression of IIMs to provide evidence for potential therapeutic targets

Summary

Introduction

Idiopathic inflammatory myopathy (IIM) is a heterogeneous group of acquired, autoimmune muscle diseases characterized by production of a spectrum of autoantibodies [including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs)], aberrant regulation of inflammatory responses, and tissue damage of different organs. Used to be mistaken for the synonyms of apoptosis, essentially PCD incorporates autophagy-dependent cell death and programmed necrosis [7] (such as NETosis, pyroptosis, ferroptosis and necroptosis) (Figure 1). Resistance exercise (RE) has been demonstrated to reduce Ab accumulation in chloroquine (CQ)induced rat model of IBM, inhibiting mitochondrial-mediated apoptosis of myofibers and improving mitochondrial function through increased mitochondrial biogenesis, upregulated mitophagy, and activated sirtuin 3 signaling [42].

Results

Conclusion