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. 2022 Jan 24;8:833114. doi: 10.3389/fmed.2021.833114

Figure 1.

Figure 1

The proposed IFN I-mediated cellular pathology in MDA5+ DM. In individuals with a background of susceptibility genes (HLA-DRB1*0101 and *0405, HLA-DRB1*0401 and *1202, or a variant in WDFY4), the dsRNA of unknown viral trigger is sensed by MDA5, causing the aberrant production of type I IFN by pDCs. Type I IFN enhances the antigen presentation of DCs, the effector function of T and B cells, and antibody production by plasma cells. Anti-MDA5 antibodies are generated in large amounts and then recognize MDA5, forming RNA-containing ICs. The ICs can activate type I IFN production via TLR7. All this promotes continued type I IFN production that sustains pathogenesis by a process with features of a vicious circle. Moreover, monocyte and macrophage may contribute to the development of RP-ILD. IFN, interferon; MDA5+ DM, anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis; pDCs, plasmacytoid dendritic cells; DCs, dendritic cells; ICs, immune complexes; TLR, toll-like receptor; RP-ILD, rapid progressive interstitial lung disease. The figure is created with BioRender.com.