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

Although 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...

Full description

Saved in:
Bibliographic Details
Published in:Immunologic research 2024-06, Vol.72 (3), p.383-394
Main Authors: Chen, Dianhui, Mo, Feng, Liu, Meiling, Liu, Lin, Xing, Junmin, Xiao, Wei, Gong, Yumei, Tang, Shanni, Tan, Zhengrong, Liang, Guikuan, Xie, Hongyan, Huang, Jun, Shen, Juan, Pan, Xingfei
Format: Article
Language:English
Subjects:
Allergology
Apoptosis
Autophagy
Biomedical and Life Sciences
Biomedicine
CD25 antigen
CD69 antigen
Cell death
CX3CR1 protein
Flow cytometry
Gene sequencing
Immunology
Infections
Internal Medicine
Inverse agonists
Kinases
Lymphocytes
Lymphocytes T
Medicine/Public Health
Molecular modelling
NF-κB protein
Original
Original Article
PD-1 protein
Plasmodium yoelii
Spleen
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although 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 the Plasmodium yoelii nigeriensis ( P. yoelii NSM)-infected mice . Flow cytometry and single-cell RNA sequencing (scRNA-seq) were performed. An inverse agonist of RORα, 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 following Plasmodium 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 selective synthetic inhibitor. Collectively, these data suggest that RORα-mediated attenuation of NF-κB signaling may be fundamental for PD-1-expressing γδT cells to modulate host immune responses in the spleen of Plasmodium yoelii nigeriensis –infected C57BL/6 mice, and it requires further investigation.
ISSN:0257-277X
1559-0755
1559-0755
DOI:10.1007/s12026-023-09441-w