025 Interstitial lung disease based on autoimmunity against melanoma differentiation-associated gene 5

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis is characterized by amyopathic DM with interstitial lung disease (ILD). Here, we investigated whether autoimmunity against MDA5 has a pathological role in the development of ILD. C57BL/6 mice were immunized emulsion including recombinant mouse whole protein once week for 4 times. The MDA5-immunized intranasally administrated polyinosinic-polycytidylic acid [poly (I:C)] at same time last immunization. MDA5-reactive T cells and anti-MDA5 antibodies developed MDA5-immunizd mice, which ILD-like consisting respiratory CD4+T cell-rich inflammatory cell infiltration fibrotic changes day 35, while no control did (P < 0.01 Fisher's exact test). contents collagen lungs also upregulated compared to controls (mean ± standard error; 144.1 16.1 μg 60.6 6.6 μg; P 0.05 Student’s t prolonged inflammation was suppressed Rag1-knockout CD4-depleted but not CD8-depleted μMT mice. Moreover, adoptive transfer cells, IgGs, from induced recipients. Upregulated mRNA level type I interferons observed all poly (I:C)-administrated regardless MDA5, interleukin (IL)-6 levels significantly elevated throughout course those Treatment anti-IL-6 receptor antibody ameliorated change In conclusion, (I:C)-induced acute injury, resulting disease. IL-6 potential therapeutic target