Research in systemic immune-mediated rheumatic diseases (IMRDs)—including systemic lupus erythematosus (SLE), Sjögren’s syndrome, systemic sclerosis, inflammatory myopathies, and vasculitis—has entered an era of profound transformation. Advances in mechanistic immunology, propelled by high-resolution genomics, spatial and single-cell profiling, and systems immunology approaches, have sharply clarified the complex and dynamic pathways that drive these conditions. This new understanding has rapidly begun to close persistent knowledge gaps about disease heterogeneity and treatment resistance, while offering the field increased translational opportunities. Recent evidence demonstrates that many of these pathogenic mechanisms are not just academic discoveries but viable targets for new and emerging therapies. Nonetheless, challenges remain, particularly in translating molecular findings into routine clinical practice, refining patient stratification, and matching the right therapeutic agent to individualized disease profiles.

This Research Topic aims to advance understanding of both classical and newly discovered pathogenic pathways in IMRDs that are amenable to specific intervention. By highlighting links between mechanistic insights and tangible therapeutic development, the objective is to foster contributions that bridge the gap from bench to bedside. The focus is on molecular and cellular routes where targeted molecules or biologics are already in late-stage clinical development or hold strong promise for near-term advancement. Our goal is to surface work that paves the way for more effective, personalized treatments—especially in diseases like SLE, where translational progress is most pronounced—and to encourage studies proposing biomarkers for response prediction or stratification.

The thematic range of this Research Topic is limited to mechanisms and pathways for which targeted therapies are clinically actionable or under active evaluation. More speculative or preclinical themes outside of this translational scope are not prioritized. We invite submissions exploring, but not limited to, the following themes:

- Interferon signaling, nucleic acid sensing, and clinical translation of the cGAS–STING pathway

- Modulation of co-stimulation and immune synapse, including the CD40–CD40L axis

- Precision JAK/TYK signaling approaches and their relation to molecular/clinical endotypes

- Lymphocyte trafficking and S1P1 modulation in disease activity and organ involvement

- B-cell ontogeny, survival, and emerging therapies targeting BLyS/BAFF/TACI and CAR-T cell approaches

- Inhibition of endosomal Toll-like receptor (TLR) pathways and downstream interferon effects

- Immunoglobulin recycling via FcRn inhibitors, with insights into pharmacodynamics and safety management

- Translational extension of these mechanisms and therapeutics across other IMRD subtypes

We welcome original research, brief reports, reviews, systematic reviews, and perspectives that marry mechanistic rationales to imminent or ongoing therapeutic relevance.

Are you interested in contributing a manuscript to this Research Topic?

Advances in pathogenetic mechanisms of immune-mediated rheumatic diseases with forthcoming therapeutic implications