The landscape of cellular immune alteration in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-organ inflammation and profound immune dysregulation. Aberrant interactions among adaptive and innate immune cells-including T cells, B cells, dendritic cells, macrophages, neutrophils, and natural killer cells-disrupt immune tolerance and perpetuate chronic inflammation. This review provides a comprehensive overview of the dysfunctional cellular immune landscape in SLE, focusing on the pathogenic crosstalk among immune cell subsets and its contribution to disease progression. We highlight the imbalance of T cell subsets (Th1, Th17, Tfh, Treg), B cell hyperactivation, and impaired regulatory cell function. Furthermore, we discuss how excessive NETosis, type I interferon signaling, and impaired apoptotic clearance amplify autoantibody production and immune complex-mediated injury. Emerging evidence positions gut microbiome dysbiosis as a critical environmental driver of immune dysregulation in SLE, characterized by depletion of beneficial butyrate-producing commensals and enrichment of pro-inflammatory taxa. This dysbiosis contributes to disease pathogenesis through gut barrier dysfunction, molecular mimicry, and short-chain fatty acid deficiency. Finally, we examine potential therapeutic strategies, including immune checkpoint modulation, metabolic interventions, and novel cellular therapies, aimed at restoring immune equilibrium in SLE.