Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs. A complex interaction of genetics, environment, and hormones leads to immune dysregulation and breakdown of tolerance to self-antigens, resulting in autoantibody production, inflammation, and destruction of end-organs. Emerging evidence on the role of these factors has increased our knowledge of this complex disease, guiding therapeutic strategies and identifying putative biomarkers. Recent findings include the characterization of genetic/epigenetic factors linked to SLE, as well as cellular effectors. Novel observations have provided an improved understanding of the contribution of tissue-specific factors and associated damage, T and B lymphocytes, as well as innate immune cell subsets and their corresponding abnormalities. The intricate web of involved factors and pathways dictates the adoption of tailored therapeutic approaches to conquer this disease.

iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling

“…LN affects 40%-60% of adult SLE patients (1) and is characterized by Ab and complement deposition in the kidneys (2,3). IC deposition initiates recruitment and activation of neutrophils and monocytes that produce inflammatory mediators to amplify injury, often resulting in irreversible loss of renal function, i.e., endstage fibrosis (4)(5)(6).…”

Key genes and functional coexpression modules involved in the pathogenesis of systemic lupus erythematosus

“…Though many progresses have been achieved in the therapy of SLE in the past two decades, it is still difficult to effectively control its progression and many patients’ prognosis is still poor (Giannelou & Mavragani, ; Leone et al, ; Paley, Strand, & Kim, ; Tektonidou, Lewandowski, Hu, Dasgupta, & Ward, ). Previous studies have identified that the etiology of SLE is multifactorial, and genetic predisposition and environmental factors both have critical roles in its pathogenesis (Moulton et al, ; Teruel & Alarcón‐Riquelme, ; Tsokos, Lo, Reis, & Sullivan, ). Despite many studies on SLE in recent years, the molecular mechanism underlying this disease is still poorly defined (Moulton et al, ; Zharkova et al, ).…”

The role of Syk in peripheral T cells

“…In a similar manner, human T cells from patients with SLE exhibit a rewiring of their T cell receptor (TCR) wherein the expression of the CD3-ζ chain is decreased, replaced by the homologous FcRγ chain, which recruits the downstream signaling Syk kinase rather than the CD3-ζ partner Zap70 (25). Other investigators have demonstrated that naïve CD4 T-cells treated with immune complexes and C5b-9 can phosphorylate TCR signaling proteins and spleen tyrosine kinase (Syk) (26) so that the FcRγ chain displaces the CD3-??…”