XCR1 + Conventional Type 1 Dendritic Cells Exacerbate the Inflammation in Osteogenic Arthritis Through IL ‐ 17A + CD8 + T Cells

Objective Ankylosing spondylitis (AS) and enthesitis‐related arthritis (ERA) are autoimmune bone diseases characterized by prominent heterotopic ossification and both have poor prognoses. The pathologic mechanisms of these diseases remain poorly understood. Methods After single‐cell RNA‐sequencing and T cell receptor (TCR) profiling, we used flow cytometry and multiplex immunofluorescence to quantify and map specific immune‐cell subsets within lesions of early rheumatoid arthritis and AS, analyzing a total of 33 patient specimens. Furthermore, we identified a peptide from versican, a chondroitin sulfate proteoglycan of ligament, to establish an AS mouse model. In the novel model, immune‐cell quantification, spatial mapping, and targeted therapies were applied to elucidate the pathogenic roles of key cellular subpopulations. Results Conventional Type 1 dendritic cells (cDC1s) were enriched in the joints of patients with ERA and exhibited a high level of major histocompatibility complex (MHC) I antigen presentation, which robustly interact with CD8 + T cells. Moreover, cDC1s, harboring the molecular of MHC I antigen presentation, were detected in spinal ligament tissue of patients with AS. In mice, versican‐derived peptide combined with Type II collagen stably and efficiently elicits a model exhibiting hallmark enthesitis and heterotopic ossification. In this model, cDC1s and IL‐17A + CD8 + T cells were highly enriched in the ligamentous synovial tissues. Blocking the recruitment of cDC1s through XCL1‐neutralizing antibody alleviates arthritis symptoms in vivo. Conclusion Thus, cDC1s promote autoimmune reactions and osteoarticular lesions through IL‐17A + CD8 + T cells. Targeting cDC1 represents a novel therapeutic target for bone remodeling arthritis. image