NIH Research Festival
After an injury, the body must establish a delicate balance between immune activation, to fight off infection and clear debris, while preventing immune reactivity to the body‚Äôs own tissue to promote optimal healing and long-term survival. During wounding and surgical material implantation for tissue reconstruction, there is a disturbance in homeostasis and release of self-antigen. Regulation between tolerance and auto-inflammation in this process is not well understood. Here, we analyzed antigen-presenting cells in muscle injury and found that pro-regenerative biomaterials enrich a novel Batf3-dependent CD103+XCR1+CD206+CD301b+ dendritic cell population associated with cross-presentation and self-tolerance. Up-regulation of E-Cadherin (the ligand for CD103) and XCL-1 in injured tissue suggests a mechanism for cell recruitment to trauma. Muscle injury recruited NK cells that produced Xcl1 when stimulated with fragmented extracellular matrix. Without cross-presenting cells T cell activation increases, pro-regenerative macrophage polarization decreases, and there are alterations in myogenesis, adipogenesis, fibrosis, and increased muscle calcification. While this pathway has been described in cancer, this is the first time it has been implicated in wound healing. These data represent a new fundamental mechanism of immune regulation that has not previously been linked to trauma and material implantation, resulting in downstream effects on tissue regeneration, having implications for both short- and long-term injury recovery.
Scientific Focus Area: Biomedical Engineering and Biophysics
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