miR-182-Mediated Dysregulation of Histidine Metabolism Compromises T Cell Immunity in Sepsis.

MicroRNA-182 (miR-182) exhibits immunomodulatory effects in regulating inflammatory responses to bacterial infection. However, the involvement of miR-182 in regulating T-cell immune function and differentiation in sepsis remains unknown. This study investigated the role of miR-182 in regulating T cell immune function and its mechanism in sepsis-induced immunosuppression. Using the cecum ligation and puncture model to mimic experimental sepsis, we found a significant reduction in splenic lymphocyte numbers and dysregulated T cell differentiation in septic mice. miR-182 expression was elevated in septic mice. Its knockout improved T cell immune function, ameliorated organ damage and improved survival rates in septic mice. Metabolomic and proteomic profiling revealed that histidine catabolism was attenuated and histidine was increased after miR-182 knockout. L-histidine supplementation alleviated T-cell immunosuppression in vivo. In addition, elevated plasma miR-182 levels were correlated with poor clinical prognosis in sepsis patients. Our findings demonstrate that miR-182 deficiency ameliorates the immunosuppression of T cells through the modulation of histidine metabolism, offering novel insights into the molecular mechanisms underlying T-cell dysfunction in sepsis.