Organoid models in autoimmune diseases: bridging phenotypic modeling and functionally informed therapeutic assessment

Autoimmune diseases exhibit substantial clinical heterogeneity, with marked variability in therapeutic responses among patients receiving identical treatment strategies. Despite ongoing advances in targeted therapies, the lack of functional platforms capable of capturing individual pre-treatment variability remains a major barrier to precision immunotherapy. This review systematically summarizes the application of organoid models in autoimmune diseases within the conceptual framework of immune microenvironments and tissue-level functional readouts. We discuss their major construction strategies, progress in mechanistic studies, and emerging roles in therapeutic response evaluation, while comparing their applicability and limitations across different disease contexts. Current evidence indicates that organoid models can preserve key aspects of tissue-specific structure and function in vitro, thereby generating reproducible functional responses to immune-related stimuli and pharmacological interventions. However, in the absence of sustained immune homeostasis and systemic regulation, organoid-derived readouts predominantly reflect tissue-intrinsic responses rather than integrated disease states. Consequently, their ability to directly predict clinical outcomes in autoimmune diseases remains limited and varies across disease types. Organoid models are best positioned as experimental platforms for dissecting immune–tissue interactions and probing tissue-level functional sensitivity. Their translational utility in therapeutic response assessment depends on careful alignment with disease-specific pathophysiology and a clear understanding of where these models are informative—and where their limitations must be acknowledged.