A critical look at animal and cellular models in autoinflammatory diseases.

Autoinflammatory diseases (AIDs) comprise a diverse group of conditions arising from dysregulated immune control due to congenital or acquired genetic abnormalities in innate immune pathways, and patients typically require lifelong treatment. Owing to their rarity, access to patient samples is limited, making animal and cellular models indispensable for elucidating pathogenesis and advancing therapeutic development. Nevertheless, robust animal and cell-based models remain scarce. Recent advances in precision genome editing now enable lineage- and cell type-specific modeling of autoinflammation, steadily improving the fidelity with which disease phenotypes are recapitulated. In this review, we survey the current landscape of CRISPR-enabled knock-in/knock-out animal models, engineered cell lines, and patient-derived induced pluripotent stem cells for AIDs, and discuss how these platforms can be leveraged to dissect disease mechanisms and accelerate drug discovery.