Type I interferons in health and disease: molecular aspects and clinical implications

Type I interferons (IFNs), particularly IFNα and IFNβ, play a crucial role in the human immune response against viral infections. This review delves into the multifaceted antiviral, immunomodulatory, and antitumor physiological roles of type I IFNs, while describing their contribution to the pathogenesis of various disease pathologies including cancer, systemic and organ-specific autoimmunity, neuroinflammation, and atherosclerosis. Genetic determinants influencing activation of type I IFN pathways and therapeutic interventions either targeting or stimulating these pathways in the context of autoimmunity and cancer, respectively, are also discussed. Ultimately, the current understanding of the role of type I IFNs as biomarkers indicative of distinct clinical and serological phenotypes, their correlation with disease activity, their predictive role in therapeutic outcomes across diverse clinical scenarios, as well as the challenges associated with their implementation in clinical practice, are thoroughly addressed. Together, these insights underscore the significant potential of type I IFNs, as mediators and therapeutic targets, to reshape clinical decision-making, while highlighting the urgent need for robust, standardized methodologies for assessment of type I IFNs and their integration into routine practice.