Modulating the systemic and local adaptive immune response after fracture improves bone regeneration during aging

Tissue injury leads to the well-orchestrated mobilization of systemic and local innate and adaptive immune cells. During aging, immune cell recruitment is dysregulated, resulting in an aberrant inflammatory response that is detrimental for successful healing. Here, we precisely define the systemic and local immune cell response after femur fracture in young and aging mice and identify increased toll-like receptor signaling as a potential culprit for the abnormal immune cell recruitment observed in aging animals. Myd88, an upstream regulator of TLR-signaling lies at the core of this aging phenotype, and local treatment of femur fractures with a Myd88 antagonist in middle-aged mice reverses the aging phenotype of impaired fracture healing, thus offering a promising therapeutic target that could overcome the negative impact of aging on bone regeneration.

Automated summary

Tissue injury triggers immune cell mobilization, but during aging, this process becomes dysregulated, leading to harmful inflammatory response. Toll-like receptor signaling appears to be responsible for the abnormal immune cell recruitment in aging animals. By targeting Myd88, a key regulator in TLR signaling, the impaired fracture healing caused by aging can be reversed, offering a potential therapeutic target for bone regeneration.