The study aimed to analyze the single-cell transcriptomes of immune cells in juvenile idiopathic arthritis (JIA) patients to understand the cellular heterogeneity within the immune system. Peripheral blood samples from fourteen JIA patients and four healthy individuals were subjected to single-cell RNA sequencing. Various subtypes of JIA were included in the patient cohort. Functional analyses, such as pseudotime trajectories and cell communication studies, were conducted to uncover immune cell changes in JIA patients. Results showed disrupted interferon and acute inflammatory responses in most cell types of JIA patients, with particularly intense responses in systemic JIA (sJIA) patients versus non-sJIA patients. Pseudotime analysis of CD4+ T, CD8+ T, B, and myeloid cells revealed that the functions of each cytokine production, cytotoxicity, and the processing and presentation of antigens were progressively strengthened, while the regulation of nuclear factor kappa B (NF-κB)-related pathways was weaker in CD4+ T and CD8+ T cells than in non-JIA. Reclustering analysis of myeloid cells highlighted interferon-related functions predominantly in non-classical monocytes of sJIA patients. Additionally, cell communication analysis identified unique ligand–receptor pairs in sJIA, suggesting potential roles in disease progression. In conclusion, interferon disorders are evident across various immune cell types in JIA patients, with stronger responses observed in sJIA patients. The ligand–receptor pairs involving migration inhibitory factor (MIF) and CXCR7/CD44 may contribute to differing joint symptoms between sJIA and non-sJIA patients. Moreover, non-classical monocytes and the CXCR2 receptor in MIF signaling may play crucial roles in sJIA progression.
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Open Access
Full Length Article
Issue
To investigate the mechanisms of 1,25（OH）2D3 on joint inflammation and bone destruction in a mouse model of collagen-induced arthritis（CIA）.
Thirty DBA/1J mice were equally allocated into control, CIA and intervention（VD）groups. The CIA model was established in the mice in the CIA group and VD group, meanwhile the VD group was treated with 1,25（OH）2D3. The thickness of the hindfoot paws was measured with vernier caliper. Micro-CT scanning was used to measure bone mineral density（BMD）of the hindfoot paw, ELISA was employed to detect the serum levels of 1,25（OH）2D3 and proinflammatory cytokines（IL-1β, IL-6, TNF-α）, and flow cytometry was performed to calculate the ratio of Th17 to Treg cells in the spleen. The pathological changes of the knee joint were observed with HE staining. Western blotting was applied to detect the expression levels of osteoprotegerin（OPG）, receptor activator of nuclear factor-κB ligand（RANKL）, NF-κB, and vitamin D receptor（VDR）in mouse ankle joints.
1,25（OH）2D3 did not reduce the incidence of CIA in the of mice in the VD group, but significantly reduced joint inflammation. Obviously decreased thickness of the hindfoot paw, arthritis score, and knee histological synovitis score（HSS）were observed in the VD group than the CIA group（all P<0.05）. The CIA group presented more serious bone destruction and lower BMD and bone volume fraction（BV/TV）when compared with the VD group（both P<0.05）. The serum levels of IL-1β, IL-6 and TNF-α and ratio of Th17/Treg cells in the VD group were statistically lower than those in the CIA group（all P<0.05）. Compared with the CIA group, the VD group had notably higher protein levels of VDR and OPG, lower levels of NF-κB and RANKL, and reduced RANKL/OPG ratio in the ankle joint（all P<0.05）.
1,25（OH）2D3 may alleviate arthritic inflammation and suppress bone destruction in the mouse CIA model via regulating the Th17/Treg ratio and the RANKL/OPG axis.
Open Access
Review Article
Issue
Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory rheumatic diseases in children, with onset before age 16 and lasting for more than 6 weeks. JIA is a highly heterogeneous condition with various consequences for health and quality of life. For some JIA patients, early detection and intervention remain challenging. As a result, further investigation of the complex and unknown mechanisms underlying JIA is required. Advances in technology now allow us to describe the biological heterogeneity and function of individual cell populations in JIA. Through this review, we hope to provide novel ideas and potential targets for the diagnosis and treatment of JIA by summarizing the current findings of single-cell RNA sequencing studies and understanding how the major cell subsets drive JIA pathogenesis.
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