eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2026-06-22 23 2 59114 article Priya Suresh Satav 1 Kishor Otari 1 Ajay Kale 1 Department of Pharmacology, Navsahyadri Institute of Pharmacy, Pune, India Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation, autoantibody production, and multisystem inflammation. A hallmark feature of SLE is persistent activation of the type I interferon (IFN-I) pathway, commonly known as the interferon signature. Plasmacytoid dendritic cells are the major source of IFN-α and contribute to sustained immune activation through nucleic acid–containing immune complexes. IFN-I signaling enhances dendritic cell maturation, promotes T helper 1 polarization, and supports survival and activation of autoreactive B cells through BAFF and APRIL pathways. Therapeutic approaches targeting BAFF and IFNAR1 have demonstrated reductions in disease activity and flare frequency, particularly in patients with high interferon activity. However, infection risk remains an important limitation of these therapies. This review summarizes current evidence regarding IFN-I–mediated immune dysregulation in SLE and highlights the comparative therapeutic significance of BAFF and IFNAR1 pathways in the development of precision-based treatment strategies. Plasmacytoid dendritic cells (pDCs) are the main source of IFN-α in SLE. They become aberrantly activated by immune complexes containing nucleic acids derived from apoptotic debris. This activation sustains IFN-I signaling and drives a cascade of immune responses. These include dendritic cell maturation, T helper 1 (Th1) polarization, and the survival and expansion of autoreactive B cells. The IFN-I pathway also enhances B-cell activation through BLyS/BAFF and APRIL signaling, promoting increased autoantibody production. Together, these processes establish a self-amplifying autoimmune loop that contributes to disease progression. Therapeutic strategies targeting these pathways have shown encouraging clinical outcomes. Inhibition of BAFF and blockade of the interferon receptor subunit IFNAR1 have been associated with reductions in disease activity and flare frequency, along with improved control of organ involvement. However, these benefits must be balanced against an increased risk of infections, reflecting the immunomodulatory effects of these therapies. This review synthesizes current evidence on the role of type I interferons in SLE pathogenesis, with particular emphasis on the distinct yet complementary roles of BAFF and IFNAR1 signaling pathways. It also evaluates the efficacy and safety profiles of emerging biologic therapies. A clearer understanding of how innate and adaptive immune pathways are differentially dysregulated in SLE provides a strong foundation for the development of more precise, targeted treatment strategies. https://www.biotech-asia.org/vol23no2/redox-imbalance-and-oxidative-stress-in-diabetes-mellitus/ Autoimmunity Targeted biologic therapy; Immunity; Plasmacytoid dendritic cells (pDCs); Systemic lupus erythematosus (SLE); Type I interferon (IFN-I)