Recent insights into the role of innate immunity in lupus.

Abstract

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder characterized by loss of self-tolerance to nucleic acids, resulting in multisystem inflammation and organ damage. The genetic underpinning of SLE spans from common risk variants with modest effect sizes to rare monogenic mutations with high penetrance. Recent advances in next-generation sequencing and transcriptomic profiling have illuminated the central role of innate immune pathways in disease pathogenesis. This review synthesizes emerging evidence regarding innate immunity in SLE, with emphasis on toll-like receptor (TLR) signaling and regulatory mechanisms, NLRP3 inflammasome activation, myeloid cell dysregulation, and microbiome-immune interactions. Understanding these pathways provides a foundation for developing targeted therapeutics that may offer precision medicine approaches for this heterogeneous disease.