T cells heal bone fractures with help from the gut microbiome
Rajeev Aurora, Matthew J. Silva
Rajeev Aurora, Matthew J. Silva
Published April 17, 2023
Citation Information: J Clin Invest. 2023;133(8):e167311. https://doi.org/10.1172/JCI167311.
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Commentary

T cells heal bone fractures with help from the gut microbiome

Abstract

Immune cells play an important functional role in bone fracture healing. Fracture repair is a well-choreographed process that takes approximately 21 days in healthy mice. While the process is complex, conceptually it can be divided into four overlapping stages: inflammation, cartilaginous callus formation, bony callus formation, and remodeling. T cells play a key role in both the cartilaginous and bony callus phases by producing IL-17A. In this issue of the JCI, Dar et al. showed that T cells were recruited from the gut, where the gut microbiota determined the pool of T cells that expressed IL-17A. Treatment with antibiotics and dysbiosis reduced the expansion of IL-17–expressing CD4+ T cells (Th17) and impaired callus formation. These findings demonstrate crosstalk among the gut microbiota, the adaptive immune system, and bone that has clinical implications for fracture healing.

Authors

Rajeev Aurora, Matthew J. Silva

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Figure 1

T cell subsets have a regulatory role in the inflammatory phase of fracture healing.

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T cell subsets have a regulatory role in the inflammatory phase of fract...
The findings of Dar et al. (6) show that bone fractures recruit gut-resident T cells. The strength of the inflammatory response by T cells determines the quality of callus formation and biomechanical strength. Bone fractures result in the release of sphingosine-1-phosphate. The gut microbiota determines the pool and expansion of Th17 cells. Th17 cells migrate to the callus. Callus γδ T cells and recruited Th17 cells contribute to callus formation and the anabolic stage of fracture repair.