Extracellular vesicle-associated PD-L1 induces CD4 T cell dysfunction and contributes to immunosuppression in sepsis.
1/5 보강
[BACKGROUND] The upregulation of PD-1 on T lymphocytes is one of the key mechanisms driving sepsis-induced immunosuppression.
APA
Huang J, Xia Y, et al. (2026). Extracellular vesicle-associated PD-L1 induces CD4 T cell dysfunction and contributes to immunosuppression in sepsis.. Cell communication and signaling : CCS, 24(1). https://doi.org/10.1186/s12964-026-02724-3
MLA
Huang J, et al.. "Extracellular vesicle-associated PD-L1 induces CD4 T cell dysfunction and contributes to immunosuppression in sepsis.." Cell communication and signaling : CCS, vol. 24, no. 1, 2026.
PMID
41668092
Abstract
[BACKGROUND] The upregulation of PD-1 on T lymphocytes is one of the key mechanisms driving sepsis-induced immunosuppression. Nevertheless although it is known that PD-L1 on antigen-presenting cells acts as a ligand for PD-1 on T lymphocytes, it remains to be determined whether extracellular vesicle-associated PD-L1 also serves as its ligand.
[METHODS] Plasma extracellular vesicles (EVs) were isolated via ultracentrifugation. We evaluated the relationship of EV-associated PD-L1 level to immune function and prognosis in septic patients. Additionally, we observed the effect of EV-associated PD-L1 on the proliferation and immune function of co-cultured CD4 T cells We further verified the role of EV-associated PD-L1 by knocking down PD-L1 in a mouse model.
[RESULTS] The peripheral circulating EV levels were significantly increased in septic patients compared with healthy volunteers. Enhanced PD-L1 protein content on these EVs was evident in septic patients, particularly in those exhibiting adverse prognostic features and pronounced immunosuppression. EVs secreted by LPS-stimulated monocytes were enriched with more PD-L1 than monocytes alone. Co-culture of CD4 T cells with sepsis-derived EVs significantly downregulated the expression of CD69, IFN-γ and cell viability but upregulated the level of IL-4 and TGF-β. This was accompanied by heightened PD-1 expression and an increased Tregs/CD4 T cell ratio. Conversely, this effect was partially reversed by inhibition of EV production or knockout of PD-L1 in EVs. Compared with LPS-treated EVs, PD-L1 knockout LPS-treated EVs alleviated the immunosuppressive state in CLP mice.
[CONCLUSION] The elevated level of circulating EV-associated PD-L1 was closely associated with poor prognosis and immunosuppression in septic patients. EV-associated PD-L1 engaged CD4 T cells to induce CD4 T cell dysfunction and may be one of the key mechanisms inducing immunosuppression in sepsis.
[GRAPHICAL ABSTRACT] [Image: see text]
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12964-026-02724-3.
[METHODS] Plasma extracellular vesicles (EVs) were isolated via ultracentrifugation. We evaluated the relationship of EV-associated PD-L1 level to immune function and prognosis in septic patients. Additionally, we observed the effect of EV-associated PD-L1 on the proliferation and immune function of co-cultured CD4 T cells We further verified the role of EV-associated PD-L1 by knocking down PD-L1 in a mouse model.
[RESULTS] The peripheral circulating EV levels were significantly increased in septic patients compared with healthy volunteers. Enhanced PD-L1 protein content on these EVs was evident in septic patients, particularly in those exhibiting adverse prognostic features and pronounced immunosuppression. EVs secreted by LPS-stimulated monocytes were enriched with more PD-L1 than monocytes alone. Co-culture of CD4 T cells with sepsis-derived EVs significantly downregulated the expression of CD69, IFN-γ and cell viability but upregulated the level of IL-4 and TGF-β. This was accompanied by heightened PD-1 expression and an increased Tregs/CD4 T cell ratio. Conversely, this effect was partially reversed by inhibition of EV production or knockout of PD-L1 in EVs. Compared with LPS-treated EVs, PD-L1 knockout LPS-treated EVs alleviated the immunosuppressive state in CLP mice.
[CONCLUSION] The elevated level of circulating EV-associated PD-L1 was closely associated with poor prognosis and immunosuppression in septic patients. EV-associated PD-L1 engaged CD4 T cells to induce CD4 T cell dysfunction and may be one of the key mechanisms inducing immunosuppression in sepsis.
[GRAPHICAL ABSTRACT] [Image: see text]
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12964-026-02724-3.
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