Downregulation of regulatory T cell function in patients with delayed fracture healing

摘要

Summary Bone fracture healing is a multistage regenerative process that requires the collaboration of various cell types, with approximately 5%‐10% of fractures not healing properly. Accumulating evidence suggests that dysregulations in the immune system are associated with defective healing. In a cohort of 30 bone fracture patients between 50 and 62?years of age, 8 patients displayed delayed healing. Compared to the 22 normal healing patients, these 8 delayed healing patients presented significantly lower frequencies of CD 4 + CD 25 hi Foxp3 + canonical regulatory T cells immediately following bone fracture and early on during the healing process. The CD 4 + CD 25 +/hi T cells from delayed healing patients also presented reduced capacity to express transforming growth factor beta ( TGF ‐β), and presented reduced surface expression levels of inhibitory molecules, including CTLA ‐4 and Lag‐3, compared to CD 4 + CD 25 +/hi T cells from normal healing patients. Moreover, CD 4 + CD 25 +/hi T cells from delayed healing patients were less potent in the suppression of CD 4 + CD 25 ? autologous conventional T cell proliferation, and presented reduced expansion capacity in response to interleukin ( IL )‐2 stimulation. Overall, our results demonstrated multiple reductions in regulatory T cell function in delayed healing patients that could produce long‐lasting consequences in the bone fracture healing process.