A role for γ/δ T cells in a mouse model of fracture healing
Open Access
- 28 May 2009
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 60 (6), 1694-1703
- https://doi.org/10.1002/art.24520
Abstract
Objective Fractures can initiate an immune response that disturbs osteoblastic and osteoclastic cellular homeostasis through cytokine production and release. The aim of our study was to investigate γ/δ T cells, innate lymphocytes known to be involved in tissue repair, as potential cellular components of the osteoimmune system's response to an in vivo model of bone injury. The absence of such cells or their effector cytokines influences the fate of other responder cells in proliferation, differentiation, matrix production, and ultimate callus formation. Methods Tibia fractures were created in 60 γ/δ T cell–deficient mice (also called δ T cell receptor [TCR]–knockout mice) and 60 control C57BL/6 mice. Analysis included radiographs, basic histology, mechanical testing, flow cytometry, and immunohistochemical localization of γ/δ TCR–positive subsets from control animals and of CD44 expression from both groups, as well as enzyme‐linked immunosorbent assay for the effector cytokines interleukin‐2 (IL‐2), interferon‐γ (IFNγ), and IL‐6. Results Animals deficient in γ/δ T cells demonstrated more mature histologic elements and quantitative increases in the expression of major bone (bone sialoprotein) and cartilage (type II collagen) matrix proteins and in the expression of bone morphogenetic protein 2 at a critical reparative phase. Moreover, only γ/δ T cell–deficient animals had a decrease in the osteoprogenitor antiproliferative cytokines IL‐6 and IFNγ at the reparative phase. The result was improved stability at the repair site and an overall superior biomechanical strength in γ/δ T cell–deficient mice compared with controls. Conclusion The evidence for a role of γ/δ T cells in the context of skeletal injury demonstrates the importance of the immune system's effect on bone biology, which is relevant to the field of osteoimmunology, and offers a potential molecular platform from which to develop essential therapeutic strategies.Keywords
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