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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...
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Published in: | Immunologic research 2024-06, Vol.72 (3), p.383-394 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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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. |
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ISSN: | 0257-277X 1559-0755 1559-0755 |
DOI: | 10.1007/s12026-023-09441-w |