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.

Figure 1. T cell subsets have a regulatory role in the inflammatory phase of fracture healing.

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.