Development of early diagnostic strategies by targeting CXCR3 following heart transplantation

Abstract

Early diagnosis and treatment of acute rejection are crucial for prolonging graft survival in heart transplantation, yet no highly effective method exists for its timely detection. In this study, we identified CXCR3 as a T cell-specific biomarker via single-cell RNA sequencing of cardiac allografts and developed a nanoparticle-based fluorescent probe (CXCR3-NP) targeting CXCR3 to evaluate its diagnostic efficacy using in vivo imaging. Results demonstrated upregulated CXCR3 expression in T cells within acutely rejected tissues, validated in murine models and clinical samples, and the probe effectively bound to CXCR3 + T cells with fluorescence intensity increasing progressively during rejection. Furthermore, CXCR3-blocking antibody treatment alleviated acute rejection and reduced CXCR3 + T cell infiltration, leading to a significant decrease in CXCR3-NP fluorescence in grafts, thereby confirming the probe's high sensitivity in detecting diminished immune cell activity. This study developed a CXCR3-specific fluorescent probe for diagnosing acute rejection, with its sensitivity validated in a murine heart transplantation model showing alleviated acute rejection. Our findings provide novel insights into diagnostic strategies for cardiac allograft rejection.