Progress and unmet needs in understanding fundamental mechanisms of autoimmunity.

The rising incidence of autoimmune diseases is straining the healthcare system's capacity to care for patients with autoimmunity. To further compound this growing crisis, this rise occurs at a time when virulent infectious diseases exacerbate pre-existing conditions. Despite some novel targeted therapies introduced over the preceding decades, current treatment strategies must often fall back on non-specific immunosuppression, inflicting its own toll on patient morbidity. To improve patient care, we must re-double our efforts to understand and target the fundamental mechanisms of autoimmune disease initiation and progression. Technologic innovations have recently accelerated our ability to discover key components of the processes leading to loss of tolerance and propagation of self-tissue damage in autoimmune conditions. The special issue "Cellular and Molecular Mechanisms of Autoimmunity" highlights many of these findings through primary research and review articles which detail advances in genetics, molecular processes, cellular functions, and host-pathogen interactions. Discussion of topics ranging from non-coding RNA and the complement cascade to T-cell aging and the microbiome uncovers exciting avenues for basic and clinical investigation. Importantly, the issue seeks to focus attention on both established and emerging mechanisms of autoimmunity to ultimately help improve the specificity, safety, and efficacy of treatments for this group of challenging immune disorders. • Renewed focus on fundamental mechanisms of autoimmunity will aid development of effective and less toxic targeted therapies. • Newer discoveries pertaining to X chromosome dosing and non-coding RNAs reveal the potential utility of genetic screening. • Abnormalities in innate immunity components contribute to initiation and propagation of autoimmunity. • Extraneous pathogens and perturbations in the endogenous microbiome underly many key disease mechanisms. • Unique personalized medicine approaches could facilitate rebalancing of dysfunctional immune systems for individual patients. [ABSTRACT FROM AUTHOR]