Identification of regulatory natural killer cells in pediatric chronic graft-versus-host disease patients

Abstract

Abstract Chronic graft-versus-host disease (cGVHD) is the leading cause of late morbidity and mortality in pediatric patients, which is caused by dynamic interferences of multiple types of immune cells, including natural killer (NK) cells. While earlier studies have indicated the potential regulatory function of NK cells restraining pathogenic cell types, the identity of unique NK cell subsets remains unknown. We performed single-cell RNA sequencing on NK cells isolated from the PBMC of patients who developed cGVHD (3 patients) or not (4 patients). Through computational analyses, we identified distinct NK cell populations and found multiple subsets of NK cells expressing unique transcriptomes in patients who received hematopoietic stem cell transplantation (HSCT) compared to healthy individuals, with one of the NK cell subsets exclusively present in post-HSCT patients. Significantly different gene expression patterns were observed between the two groups of patients, including cytotoxicity-related genes elevated in cGVHD patients. By applying diverse statistical analyses, we were able to characterize these NK cell subsets, indicating their potential roles in the development or prevention of cGVHD. Our study defines novel subsets of protective NK cells during cGVHD. These findings are of high translational relevance and can contribute to the treatment of cGVHD patients.