Central nervous system autoimmunity and autoinflammation: insights from inborn errors of immunity

The field of inborn errors of immunity (IEIs) is experiencing rapid expansion due to advancements in genetic and molecular diagnostics. This progress has not only led to the discovery of numerous novel diseases but has also enhanced our understanding of genotype-phenotype correlations for specific defects. Central nervous system (CNS) inflammation and autoimmunity have emerged as significant features of several distinct IEIs, each arising from unique pathophysiological mechanisms. These include systemic autoinflammatory disorders, type I interferonopathies, vasculopathies, immune dysregulation syndromes, and immune defects leading to CNS infections and inflammation. Despite these advancements, there remains a need for a deeper understanding of the immune-CNS crosstalk and the identification of potential therapeutic targets. Current research is focused on elucidating the molecular mechanisms that regulate this interaction, yet gaps remain in translating these findings into effective treatments for both inherited and acquired neuroinflammatory conditions.

This Research Topic aims to explore novel findings in both known and newly identified IEIs that underlie neuroinflammation. The primary objectives include validating clinical and genetic features, unraveling the molecular mechanisms that govern immune-neuro crosstalk and inflammation, and developing targeted therapies for these disorders. By addressing these aims, the research seeks to answer critical questions about the pathophysiology of CNS autoimmunity and autoinflammation, and to test hypotheses related to potential therapeutic interventions.

To gather further insights in the complex interplay between IEIs and CNS autoimmunity, we welcome articles addressing, but not limited to, the following themes:

- Neuroinflammatory phenotypes associated with monogenic IEIs.
- Novel genetic causes of neuroinflammation and CNS autoimmunity.
- New insights on the molecular pathways involved in neuroinflammation.
- Key cell types and cytokines underlying neuroinflammation in specific IEIs.
- Potential therapeutic targets for these conditions.

Topic Editor Dr. Christopher Duncan discloses consultancy for Moderna and Synairgen. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Keywords: Neuroinflammation, inborn errors of immunity, interferonopathies, autoinflammatory disorders, hemophagocytic lymphohistiocytosis, HLH, ADA2, COPA, AGS, type I interferon defects.

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.