TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease

Endosomal toll-like receptors (TLRs), such as TLR7 and TLR9, are key mediators of autoimmunity. Systemic lupus erythematosus (SLE or lupus) and SjD are distinct diseases that are both characterized by heightened activation of TLR7 and TLR9 signaling networks that serve as potent modulators of chronic inflammation. This review will provide an overview of the role of these receptors in lupus and SjD, with a focus on recent mechanistic insights in the field. We will compare and contrast the roles of TLR7 and TLR9 in lupus and SjD, with a focus on the importance of B cell activation in disease. Moreover, we will discuss differences observed in sex-biased organ-specific disease manifestations. Finally, we will review current and emerging therapies that target endosomal TLR pathways and discuss their utility for treatment of SLE and SjD.