Degenerative joint changes following intra‐articular fracture are more severe in mice with T cell deficiency. Issue 8 (7th December 2020)

• Record Type: Journal Article
• Authors: Buchanan, Michael W.; Furman, Bridgette D.; Zeitlin, Jacob H.; Huebner, Janet L.; Kraus, Virginia B.; Yi, John S.; Olson, Steven A.
• Is Part Of: Journal of orthopaedic research. Volume 39:Issue 8(2021)
• Page Start: 1710
• Page End: 1721
• Publication Date: 2020-12-07
• Subjects: cytokines -- inflammation -- NK cells -- nude mice -- posttraumatic arthritis -- T cells; Orthopedics -- Periodicals; Musculoskeletal system -- Periodicals; 616.7
• DOI: 10.1002/jor.24899
• Languages: English
• ISSNs: 0736-0266

Abstract

Abstract: The inflammatory response to joint injury, specifically intra‐articular fracture, has been implicated in posttraumatic arthritis development. However, the role of T cells in regulating the development of posttraumatic arthritis is unclear. We hypothesized that the absence of T cells would lead to less severe posttraumatic arthritis following intra‐articular fracture. T cell‐deficient, athymic nude, and wild‐type C57BL/6NJ mice were assessed at 8 weeks following closed articular fracture. Joints were assessed using histologic scores of arthritis, synovitis, and bone morphology via micro computed tomography. Cells were profiled in whole blood via flow cytometry, and plasma and synovial fluid derived cytokines were quantified by multiplex analysis. Compared to C57BL/6NJ mice, nude mice had significantly greater histologic evidence of arthritis and synovitis. Whole blood immune cell profiling revealed a lower percentage of dendritic cells but increased natural killer (NK) cells in nude mice. Concurrently, nude mice had significantly higher levels of NK cells in synovial tissue. Concentrations of plasma interleukin 1β (IL‐1β) and tumor necrosis factor α, and synovial fluid IL‐12, IL‐17, and IL‐6 in both knees were greater in nude mice. Outcomes of this study suggest that T cells may play a protective regulatory role against the development of posttraumatic arthritis. Clinical significance: Lack of functional T cells exacerbated the development of posttraumatic arthritis following intra‐articular fracture suggesting that critical regulators of the immune responses, contained within the T cell population, are required for protection. Future research identifying the specific T cell subsets responsible for modulating disease immunopathogenesis will lead to new therapeutic targets to mitigate posttraumatic arthritis.