Elevated IL-21 and tissue-resident CD8 T cell gene signatures in the lungs of a dermatomyositis patient 4193

Abstract Description Aside from characteristic skin and muscle pathology, dermatomyositis can feature significant morbidity and mortality from interstitial lung disease (ILD). CD4 T cell-derived IL-21 may be a driver of dermatomyositis disease. IL-21 is best known as a product of follicular helper CD4 T cells stimulating B cells to promote antibody class-switching and affinity maturation. CD8 T cells can express the IL-21 receptor (IL21R), and IL-21 has been identified as a CD4 T cell-derived driver of CD8 T cell differentiation to tissue resident memory cells (TRM). In a mouse model of ILD, IL-21 has been shown to induce CD8 T cell differentiation into effector cells driving pulmonary fibrosis. We hypothesized IL-21-driven CD8 T cell differentiation is an important step in the pathogenesis of ILD in dermatomyositis. Using single-cell RNAseq data from the lungs of a dermatomyositis patient with ILD, we show lung CD8 T cells highly express IL21R compared to CD8 T cells from the lungs of healthy controls. We also performed gene set enrichment analyses using these data, finding significant enhancement in the expression of TRM genes in the CD8 T cells from the dermatomyositis lung. These data suggest IL-21 could be an important, understudied driver of ILD in dermatomyositis, and a potential therapeutic target. Specifically, IL-21 may act on CD8 T cells to drive differentiation into long-lived TRM in the tissues of dermatomyositis, likely contributing to tissue destruction and clinical pathology. Funding Sources Funding for this project was provided by the Rheumatology Research Foundation. Topic Categories Basic Autoimmunity (BA)