Single-cell RNA-seq analysis identifies the atlas of lymph fluid and reveal a sepsis-related T cell subset

The lymphoid cycle as the sentinel of immune response, its cell subtypes and immune properties and functions during sepsis are still unclear. This study described a comprehensive picture of immune cells in rat lymph fluid by single-cell RNA sequencing and identified a unique subset of CD4+ T cells (CD4_Icos) in the early state of sepsis, confirming its crucial role in Treg cell production. Transferring with CD4+Icos+ T cells significantly alleviated CLP-induced organ injury, while Icosfl/flCd4-CreERT2 mice showed reduced number of Treg and increased inflammation and mortality risk. Further screening and validation experiments identified Npas2 as an Icos-specific transcription factor that regulates Icos expression and promotes the differentiation of CD4+Icos+ T cells. Clinical results disclosed the negative correlation between the expression of ICOS in CD4+ T cells and SOFA score in septic patients, which affected the prognosis of septic patients. These findings indicated the protective role of CD4+ T cells in sepsis.