UCSF

Autoimmune disease arises from dysregulation of the immune system, leading to its attack on the body's own tissues and organs. The clinical heterogeneity of these diseases arises from several sources, such as genetic predisposition, environmental triggers, and aberrant immune responses. One emerging area of interest is the role of transposable elements (TEs) in autoimmune disease pathogenesis because these self-nucleic acids can be mistakenly detected as foreign, which can trigger a chronic immune reaction.There is growing appreciation for the role of TEs in systemic lupus erythematosus (SLE) and studies have found differentially expressed TEs in SLE patients, which suggests a link between TE activity and disease mechanisms. Our work investigated TE expression in four immune cell types from SLE patients, revealing cell-specific and SLE subphenotype-specific differentially expressed TEs, with additional cell-type-specific TE associations in different ancestry groups. TE expression was also associated with host gene expression involved in antiviral and immune responses, supporting the hypothesis that TEs could activate the innate immune system and contribute to chronic inflammation and autoimmunity. This study underscores the importance of TEs in SLE heterogeneity and highlights the need for further exploration of TE expression in normal immune cells and functional studies to understand their role in SLE pathogenesis. Future work to study whether antiretroviral drugs could reduce expression of TEs and mitigate SLE symptoms is warranted, given the potential involvement of TEs in autoimmune disease pathogenesis