Genetic and environmental determinants in autoimmune disease development and emerging therapeutic strategies

The field of autoimmune and autoinflammatory disease research is focused on unraveling the complex interactions between genetic predisposition, environmental influences, and immune regulation. Despite significant advancements, the origins of autoimmune diseases remain only partially understood, with the loss of self-tolerance leading to chronic inflammation and multi-organ pathology. Prominent genetic risk factors, including polymorphisms in major histocompatibility complex (MHC) class II and other inflammatory genes, have been consistently linked to increased susceptibility. Recent studies highlight additional contributions from environmental exposures, such as chronic viral infections—most notably Epstein–Barr virus—as well as imbalances in commensal microbiota and hormonal factors, all of which can disrupt immune homeostasis in genetically susceptible hosts. While new insights into immunometabolic regulation and adaptive immune responses are emerging, a comprehensive understanding of how genetic and environmental determinants converge to trigger disease remains elusive, hindering progress in prevention and treatment.

This Research Topic aims to advance the understanding of autoimmune and autoinflammatory disease mechanisms by fostering research that integrates genetic, environmental, cellular, and molecular perspectives. We seek to address key questions such as how antigen presentation and T-cell selection are altered in autoimmunity, the role of immunometabolic regulation in disease progression, and the efficacy of current and emerging targeted therapies. The overarching objective is to generate new mechanistic insights and translate these discoveries into innovative therapeutic strategies, ultimately improving outcomes for patients affected by these challenging disorders.

This Research Topic will cover studies that investigate the interplay between genetic predisposition, epigenetic modifications, environmental exposures, and immune dysregulation in the initiation and progression of autoimmune and autoinflammatory diseases. We invite submissions related to mechanistic research, preclinical modeling, and therapeutic interventions, while excluding those focused solely on unrelated diagnostic markers or bone metabolism unless directly connected to disease mechanisms. To gather further insights and promote multidisciplinary collaboration, we welcome articles addressing, but not limited to, the following themes:

-Genetic risk loci and immune regulation in autoimmunity
-Environmental triggers and their molecular impact on immune pathways
-Antigen presentation and T-cell clonal dynamics
-Immunometabolic networks in disease development and therapy
-Translational advances in targeted and antigen-specific therapeutic strategies
-Dysregulated adaptive and innate immune responses
-Epigenetic and transcriptomic profiles informing disease mechanisms
-Application of Artificial Intelligence in Autoimmune Disease therapeutic development

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Conceptual Analysis
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Conceptual Analysis
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Autoimmune diseases, immune tolerance, MHC class II, autoreactive T cells, immunometabolism, genetic predisposition, environmental triggers, viral infection, microbiota, CAR T-cell therapy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.