Ji Hyeon Ju

Hong Ki Min, M.D., Ph.D., Mi Ryoung Seo, M.D., Sang-Hoon Lee, M.D., Ph.D., Yeon-Ah Lee, M.D., Ph.D., Jennifer Jooha Lee, M.D., Ph.D., Seong-Ryul Kwon, M.D., Ph.D., Tae-Hwan Kim, M.D., Ph.D., Min-Chan Park, M.D., Ph.D., Kichul Shin, M.D., Ph.D., Ji Hyeon Ju, M.D., Ph.D., Yong-Gil Kim, M.D., Ph.D., Bon San Koo, M.D., Ph.D., Eun Young Lee, M.D., Ph.D., Hoon-Suk Cha, M.D., Ph.D., Seung Cheol Shim, M.D., Ph.D., Ji Hui Shin, R.N., Tae-Jong Kim, M.D., Ph.D.; on behalf of the Korean College of Rheumatology-Alliance of eXperts In Spondyloarthritis (KCR-AXIS). J Rheum Dis 2026;33:255-78. https://doi.org/10.4078/jrd.2026.0126

Autoimmune diseases—including systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA)—are increasingly understood as programmable microenvironmental states, wherein evolving changes in matrix mechanics, barrier integrity, interferon and cytokine networks, immune‐complex deposition, and stromal–immune reciprocity progressively reshape tissue behavior. These shifting axes generate nonlinear trajectories of fibrosis, vascular injury, and joint destruction that static or reductionist in vitro systems fail to recapitulate. Organoid and organ‐on‐a‐chip platforms now allow controlled reconstruction of these dynamic microenvironments in human‐derived systems. By integrating iPSC‐derived epithelial, endothelial, stromal, and immune lineages with tunable extracellular matrix (ECM) stiffness and viscoelasticity, perfusable microvasculature, and modular innate and adaptive immune components, these systems reproduce key autoimmune phenomena. These include stiffness‐driven fibroblast activation and endothelial‐to‐mesenchymal transition (EndoMT), interferon‐conditioned barrier collapse, immune‐complex‐mediated injury, and cytokine‐dependent stromal invasion. Patient‐specific induced pluripotent stem cell (iPSC), CRISPR‐based editing of risk alleles, and controlled exposure to sera or autoantibody repertoires provide genetic and immunologic personalization, while multi‐omic profiling, spatial imaging, and machine‐learning analytics enable quantitative alignment between organoid states and patient tissues. By translating pathogenic microenvironmental logic into controllable 3D systems, these platforms establish autoimmune organoids as programmable, human‐relevant tools for mechanistic discovery, therapeutic interrogation, and precision modeling—laying the groundwork for next‐generation, potentially animal‐free pipelines and advancing personalized immunology across SSc, SLE, and RA.

Sjögren’s disease (SjD) is a chronic autoimmune disease characterized by lymphocytic infiltration and dysfunction of the exocrine glands, with manifestations extending beyond glandular sicca symptoms to multiple extraglandular systems. Although the pathogenesis of SjD remains incompletely understood, growing evidence indicates that a complex cytokine network involving both innate and adaptive immune pathways plays a central role in disease development. This narrative review summarizes recent updates on cytokine signaling in SjD across three clinically relevant domains. In glandular inflammation, activation of salivary gland epithelial cells through Toll-like receptor pathways triggers type I interferon (IFN) signaling via plasmacytoid dendritic cells, while IFN-γ, Th17-related cytokines (IL-6, IL-17, IL-22), BAFF/APRIL, and chemokines (CXCL10, CXCL12, CXCL13) collectively sustain local inflammation and ectopic lymphoid organization. The BAFF/APRIL axis, a systemic type I IFN signature, and IL-21–follicular helper T cell–B cell interactions primarily drive systemic immune activation, which together underlie autoantibody production, hypergammaglobulinemia, and a lymphoma-prone phenotype. In contrast, constitutional symptoms such as fatigue, pain, and dryness frequently dissociate from classical inflammatory activity and are better explained by neuroimmune–metabolic mechanisms, including the IFN-γ–IDO–kynurenine pathway and symptom-associated proteomic signatures. Collectively, these findings underscore the heterogeneous nature of SjD, in which glandular inflammation, systemic immune activation, and constitutional symptoms are driven by distinct yet partially overlapping cytokine pathways. Recognizing this heterogeneity has direct implications for cytokine-targeted therapy, suggesting that future trials should stratify patients by disease phenotype (IFN-high, B cell-dominant, and symptom-dominant) rather than treating SjD as a uniform population.

Alcohol consumption has been associated with an increased dementia risk, including Alzheimer's disease (AD). However, the direct impact on human neuronal systems remains insufficiently characterized. We used human induced pluripotent stem cells (iPSC)-derived cortical neurons, spheroids, and cerebral organoids exposed to physiologically relevant ethanol concentrations for seven days. We assessed neuronal maturation, dendritic morphology, and electrophysiological activity, alongside molecular and functional markers related to AD pathology. Chronic ethanol exposure impaired cortical neuronal maturation and network activity and reduced dendritic complexity in human iPSC-derived cortical neurons. Notably, ethanol exposure induced an amyloidogenic shift characterized by increased amyloid-beta (Aβ)-related processing. These changes were consistently observed across both 2D cortical neurons and 3D cerebral organoid models. Our findings indicate that chronic alcohol exposure disrupts neuronal maturation and promotes Alzheimer's disease-related pathology in human iPSC-derived neuronal models. This study highlights the value of human iPSC-based platforms for investigating the cellular impact of lifestyle-associated risk factors in neurodegenerative disease.

The convergence of CRISPR genome editing, patient-derived organoids, and induced pluripotent stem cells (iPSCs) has reshaped in vitro disease modeling by enabling mechanistic investigations of human pathophysiology within genetically matched, tissue-relevant systems. Together, these technologies provide a synergistic platform for precise manipulation of disease-associated variants and support the generation of isogenic organoid models that reproduce key phenotypic and functional hallmarks across cancer, neurodegenerative, inflammatory, and monogenic disorders. In this review, we highlight how diverse CRISPR modalities—including knock-out, knock-in, CRISPRa/i, and genome-scale screening—have been applied to dissect gene function, model disease progression, and guide therapeutic development using iPSC- and organoid-based systems. We further discuss the application of these platforms in genotype- and phenotype-driven precision medicine, enabling patient stratification, drug-response prediction, and individualized treatment design. We illustrate these convergent applications with representative case studies spanning mechanistic research and early clinical translation. By combining the scalability of genome engineering with the physiological fidelity of organoids, CRISPR-integrated platforms are redefining the frontiers of experimental medicine. These approaches accelerate the discovery of disease mechanisms and actionable therapeutic targets while establishing individualized clinical strategies for complex human diseases. Collectively, they position CRISPR-enabled organoid systems as a foundational infrastructure that bridges genome editing to individualized therapy and supports next-generation precision medicine.

Induced pluripotent stem cell (iPSC)–derived chondrogenic tissues represent a promising alternative for treating cartilage defects in chronic degenerative joint conditions such as osteoarthritis (OA). Cartilage tissue has limited self-repair capacity, and although allogeneic transplantation has potential, a less invasive delivery method could enhance the efficacy of cell-based therapies. The aim of this study was to develop iPSC-derived “minimal injectable unit” chondrogenic micropellets (MIUChons) for delivery via intra-articular injections for OA therapy. To create transplantable allogeneic cartilage tissue, we optimized good manufacturing practice or clinical-grade production of iPSC-derived injectable chondrogenic spheroids and tested them in OA animal models. MIUChons were delivered to damaged cartilage through a single injection. In vivo and in vitro analyses demonstrated that MIUChon treatment effectively reduced cartilage degeneration and deterioration. In addition, injecting MIUChons into the intra-articular cavity improved arthritis symptoms. Overall, MIUChons offer a strategy for treating cartilage deterioration via intra-articular injection in patients with OA.

Red blood cells (RBCs), essential for oxygen transport and carbon dioxide removal, are pivotal for maintaining systemic metabolic homeostasis. However, glo

Jin Kyun Park, M.D., Ph.D., Byeongzu Ghang, M.D., Ph.D., Seung Woo Han, M.D., Ph.D., Ji Hyeon Ju, M.D., Ph.D.. J Rheum Dis -0001;0:. https://doi.org/10.4078/jrd.2025.0034

Hyun Jin Baek, Yoojun Nam, Yeri Alice Rim, Ji Hyeon Ju. IJSC -0001;0:. https://doi.org/10.15283/ijsc25028

Seokchan Hong, Ji Hyeon Ju, Sang-Heon Lee, Seung-Jae Hong, Sang-hyon Kim, Ga Young Ahn, Jae Hyun Jung, Jin-Wuk Hur, You-Jung Ha, Jin Kyun Park, Hyun-Sook Kim, Sung Won Lee, Yong-Beom Park, Mie Jin Lim, Yun Sung Kim, Jung Soo Song, Chan-Bum Choi, Seong-Ho Kim, In Ah Choi, Kee Don Choi, Tae Hee Lee, Young Sin Cho, Yong Chan Lee, Kye Sook Kwon, Hyejung Lee, Mihee Park, Junga Heo, Song Baek, Chang-Keun Lee. Gut and Liver -0001;0:. https://doi.org/10.5009/gnl250019