부산대학교 도서관

BACKGROUND.: Acute graft-versus-host disease (aGVHD) mediated by alloreactive T cells remains a serious and life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). The contribution of the different CD4 T helper cell subtypes to the pathogenesis and regulation of aGVHD is a central point in current research. The specialized effector subsets of T cells that differentiate from naive T cells into mature cells are closely related to scaffold/matrix-associated region-1–binding protein (SMAR1). However, the role of SMAR1 in aGVHD is unclear. METHODS.: Peripheral blood was collected from the patients with or without aGVHD after allo-HCT. The differences in CD4 T cells transduced with the SMAR1 lentivirus vector and empty vector were analyzed. A humanized aGVHD mouse model was constructed to evaluate the function of SMAR1 in aGVHD. RESULTS.: The expression of SMAR1 was significantly reduced in the CD4 T cells from aGVHD patients and related to the occurrence of aGVHD. SMAR1 overexpression in human CD4 T cells regulated CD4 T-cell subsets differentiation and inflammatory cytokines secretion and inhibited the Janus kinase/signal transducer and activator of transcription pathway. Moreover, SMAR1 changed chromatin accessibility landscapes and affected the binding motifs of key transcription factors regulating T cells. Additionally, upregulation of SMAR1 expression in CD4 T cells improved the survival and pathology in a humanized aGVHD mouse model. CONCLUSIONS.: Our results showed that upregulation of SMAR1 regulated the CD4 T-cell subpopulation and cytokines secretion and improved survival in a humanized aGVHD mouse model by alleviating inflammation. This study provides a promising therapeutic target for aGVHD.