Characteristics of splenic PD-1+ γδT cells in Plasmodium yoelii nigeriensis infection

AbstractAlthough the functions of programmed death-1 (PD-1) on αβ T cells have been extensively reported, a role for PD-1 in regulating γδT cell function is only beginning to emerge. Here, we investigated the phenotypic and functional characteristics of PD-1-expressing γδT cells, and the molecular mechanism was also explored in thePlasmodium yoelii nigeriensis (P. yoelii NSM)-infected mice. Flow cytometry and single-cell RNA sequencing (scRNA-seq) were performed. An inverse agonist of ROR α, SR3335, was used to investigate the role of RORα in regulating PD-1+γδT cells. The results indicated that γδT cells continuously upregulated PD-1 expression during the infection period. Higher levels of CD94, IL-10, CX3CR1, and CD107a; and lower levels of CD25, CD69, and CD127 were found in PD-1+γδT cells from infected mice than in PD-1−γδT cells. Furthermore, GO enrichment analysis revealed that the marker genes in PD-1+γδT cells were involved in autophagy and processes utilizing autophagic mechanisms. ScRNA-seq results showed that RORα was increased significantly in PD-1+γδT cells. GSEA identified that RORα was mainly involved in the regulation of I-kappaB kinase/NF-κB signaling and the positive regulation of cytokine production. Consistent with this, PD-1-expressing γδT cells upregulated RORα followingPlasmodium yoelii infection. Additionally, in vitro studies revealed that higher levels of p-p65 were found in PD-1+γδT cells after treatment with a RORα se...
Source: Immunologic Research - Category: Allergy & Immunology Source Type: research