The CD103-XCR1 axis mediates the recruitment of immunoregulatory dendritic cells after traumatic injury

ABSTRACT During wounding and material implantation there is a disturbance in tissue homeostasis and release of self-antigen, and regulation between tolerance and auto-inflammation in injury is not well understood. Here, we analyzed antigen-presenting cells in biomaterial-treated muscle injury and found that pro-regenerative materials enrich Batf3-dependent CD103 + XCR1 + CD301b + dendritic cells associated with cross-presentation and self-tolerance. Muscle trauma was accompanied by CD8 + iTregs and expansion of CD103 + XCR1 + CD62L - adaptive immune cells. Up-regulation of E-Cadherin (the ligand for CD103) and XCL-1 in injured tissue suggests a mechanism for cell recruitment to trauma. Without cross-presenting cells T cell activation increases, pro-regenerative macrophage polarization decreases, and muscle healing is impaired. These data describe a regulatory communication network through CD103 + XCR1 + immune cells resulting in downstream effects on tissue regeneration.