SLC16A7 Facilitates aGVHD through Regulating Calcium Influx and Lipid Metabolism of CD4 ⁺ T Cells

T cell metabolic disorders in patients with acute graft-versus-host disease (aGVHD) have been studied, but the underlying mechanisms remain poorly understood. Solute carrier (SLC) transporters play a crucial role in cell metabolism, but their involvement in T cell-mediated aGVHD has not been investigated. In this study, we observed that SLC16A7 levels were down-regulated in CD4 ⁺ T cells of both aGVHD mice and patients, which in turn increased calcium (Ca ²⁺) influx in activated CD4 ⁺ T cells and promoted the differentiation of Th1 and Th17 cells, leading to the exacerbated aGVHD cascade. Moreover, deficiency of SLC16A7 promoted calcium overload in activated CD4 ⁺ T cells through regulating SERCA3 proteins and altered characteristics of lipid metabolism, decreasing levels of oleic acid, thereby aggravating aGVHD. Interestingly, supplementation of oleic acid rescued the survival of aGVHD mice. This study characterized a previously unknown role of SLC16A7 in T cell-mediated aGVHD and provided a promising therapeutic strategy to target T cell metabolism for the alleviation of aGVHD.