Hypothetical involvement of autoantibodies in myositis. (1) An unknown trigger (for example, a viral infection) can enter the respiratory tract, leading to a modification of histidyl-tRNA synthetase in the lungs and to anti-Jo-1 production (2), which is a common finding in patients with interstitial lung disease (ILD) (antisynthetase syndrome). When immature dendritic cells (DCs) take up the pathogen (in this case, the histidyl-tRNA synthetase), they are activated and mature into effective antigen-presenting cells. (3–5) Both immature and mature DCs have been found in muscle tissue and skin of myositis patients. Additionally, plasmacytoid dendritic cells (PDCs), which are known producers of interferon-alpha (IFN-α), are highly expressed in anti-Jo-1-positive patients and IFN-α can be found in (3) muscle tissue, (4) skin, and (5) circulation of these patents. (5) High levels of both anti-Jo-1 and IFN-α are correlated with disease activity. (6) Autoantigens (histidyl-tRNA synthetase and Mi-2) are expressed in muscle tissue, especially in regenerating fibres. Moreover, major histocompatibility complex (MHC) class I is also known to be expressed in regenerating fibres and PDCs are often expressed adjacent to MHC class I-positive muscle fibres. (7) High BAFF levels have also been characterised in the circulation of anti-Jo-1-positive patients together with the expression of B cells and plasma cells that possibly could locally produce autoantibodies and function as autoantigen-presenting cells in a subset of patients. Anti-Jo-1, antihistidyl-tRNA synthetase antibody; BAFF, B cell-activating factor of the tumour necrosis factor family. Partly adapted from Servier Medical Art.