Innate immunity in SLE pathogenesis

Abstract A growing body evidence supports the role of innate immune cells, including dendritic cells (DCs) and monocytes, in the pathogenesis of systemic lupus erythematosus (SLE). The innate immune cells can sense pathogen-associated molecular patterns and danger-associated molecular patterns (DAMPs) originating from pathogens and stressed host cells, respectively, via germline-encoded pattern-recognition receptors (PRRs) such as Toll-like receptors (TLRs). Indeed, a set of PRRs can recognize self nucleic acids in the form of the lupus autoantigens dsDNA and RNA-containing ribonucleoproteins like U1-small ribonucleoprotein. While DCs and monocytes serve as antigen-presenting cells, they can produce an array of cytokines, which are dysregulated in lupus, in response to self nucleic acids through activating multiple inflammatory pathways, including TLRs, nuclear factor kappa B, interferon regulatory factors, and inflammasomes. Such inflammatory events can be furthered by cell intrinsic alterations affecting these pathways in lupus DCs and monocytes, conferring augmented responses to DAMPs. These findings embrace the consideration of targeting innate immune cells, their molecular pathways, and cytokines in treating SLE.