Autoimmune diseases exhibit substantial clinical heterogeneity, with marked variability in therapeutic responses among patients receiving identical treatment strategies. Despite the rapid development of biologics and targeted small-molecule therapies, current treatment selection largely relies on empirical approaches. A major barrier to precision immunotherapy lies in the lack of functional platforms capable of capturing individual variability prior to treatment. In this context, organoid technology has emerged as a promising human-derived model system with the potential to bridge disease modeling and therapeutic evaluation.

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 the major strategies for organoid construction, including stem cell–derived and patient-derived systems, and examine their roles in mechanistic studies, immune microenvironment reconstruction, and therapeutic response assessment. Furthermore, we compare their applicability and limitations across different autoimmune disease contexts.

Current evidence indicates that organoid models can preserve key aspects of tissue-specific architecture and function in vitro, enabling reproducible responses to immune-related stimuli and pharmacological interventions. These models provide valuable platforms for investigating immune–tissue interactions and tissue-intrinsic responses. However, due to the lack of sustained immune homeostasis, systemic regulation, and long-term immune–tissue co-adaptation, organoid-derived readouts predominantly reflect localized or transient responses rather than integrated disease states. Consequently, their capacity to directly predict clinical outcomes remains limited and varies depending on disease-specific pathophysiology. Notably, organoid models show greater translational potential in diseases where key pathological processes are closely linked to tissue-level functional alterations.

Organoid models are best positioned as experimental platforms for dissecting immune–tissue interactions and probing tissue-level functional sensitivity in autoimmune diseases. Their translational utility in therapeutic response assessment depends on careful alignment with disease-specific mechanisms and a clear understanding of their scope and limitations. Rather than serving as standalone predictive tools, organoids function as intermediate systems linking molecular mechanisms, tissue function, and clinical outcomes, thereby contributing to the advancement of precision immunotherapy.