Personalized and Precision Medicine Journal

Abstract Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by immune dysregulation and multi-organ involvement. Central to its pathogenesis is the CD154/CD40 signaling axis, which orchestrates key immunological processes, including T-B cell collaboration, dendritic cell activation, and cytokine production. Recent findings have expanded the scope of CD154 beyond its classical receptor CD40, identifying integrins as alternative receptors, thus broadening its biological impact. These discoveries underline the complexity of CD154's role in SLE and its potential as a therapeutic target. First-generation CD154/CD40-targeted therapies showed promise but were hindered by thromboembolic complications. However, second-generation therapeutics, including monoclonal antibodies, small molecules, and gene-editing technologies, exhibit improved safety and efficacy profiles. This review delves into the molecular and cellular mechanisms of CD154 in SLE, explores its emerging roles through integrin interactions, and evaluates the therapeutic advancements targeting this axis. The findings highlight CD154 as a central mediator in SLE pathogenesis and a compelling target for innovative treatment strategies.

Abstract  Autoimmune diseases (AIDs) are characterized by the immune system’s maladaptive response against self-antigens, culminating in chronic inflammation and progressive tissue damage. Although genetic predisposition establishes baseline susceptibility, environmental pollutants—such as heavy metals, pesticides, fine particulate matter (PM2.5), and industrial chemicals—are increasingly recognized as pivotal triggers of immune dysregulation. These xenobiotics induce oxidative stress, disrupt immune tolerance by impairing regulatory T-cell function, and modulate critical signaling pathways including NF-κB, MAPK, and JAK-STAT. Epidemiological studies corroborate associations between pollutant exposure and heightened incidence or severity of conditions such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. This review synthesizes molecular, cellular, and population-based evidence to elucidate the mechanisms by which environmental pollution contributes to the onset and progression of AIDs.