Dysfunctional Dendritic Cells in Radiation-Induced Jaw Injury: Insights From Single-Cell Transcriptomic Analysis of the Osteoimmune Microenvironment.

Abstract

Radiation-induced jaw injury is a serious and debilitating complication following head and neck radiotherapy (RT). The irradiation process triggers the recruitment and maladaptive activation of immune cells, thereby disrupting the delicate homeostasis of the jawbone. Despite its clinical significance, a comprehensive understanding of the osteoimmune microenvironment involved in underlying radiation-induced jaw injury remains incompletely understood. In this study, we comprehensively profiled the transcriptional landscape of mandibular bone marrow at single-cell resolution using single-cell RNA sequencing (scRNA-seq). Our analysis revealed a marked infiltration of conventional dendritic cells (cDCs). A specific subcluster of migratory dendritic cells (migDCs) characterised by the expression of genes related to maturation, migration and immune regulation was annotated. Following RT, these migDCs migrated to the draining lymph nodes. However, reduced secretion of neutrophil-derived secreted phosphoprotein 1 (SPP1) was found to impair migDC development through the SPP1/CD44/NF-κB signalling pathway, leading to an immature cDC phenotype. We also observed weakened intercellular interactions between cDCs and T cells, contributing to an imbalanced and immunosuppressive osteoimmune microenvironment after radiation exposure. Overall, our study highlights the critical role of decreased SPP1 in modulating migDC function and its subsequent impact on jawbone immune dynamics following RT.