Mesenchymal Stromal Cells Inhibit Aerobic Glycolysis in Activated T Cells by Negatively Regulating Hexokinase II Activity Through PD-1/PD-L1 Interaction

Kawasaki, Yasufumi; Sato, Kazuya; Mashima, Kiyomi; Nakano, Hirofumi; Ikeda, Takashi; Umino, Kento; Morita, Kaoru; Izawa, Junko; Takayama, Norihito; Hayakawa, Hiroko; Tominaga, Kaoru; Endo, Hitoshi; Kanda, Yoshinobu

doi:10.1016/j.jtct.2020.11.012

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…Furthermore, in a delayed-type hypersensitivity mouse model, murine MSCs expressing HIF-1α were again shown to reduce the frequency of pro-inflammatory Th17 cells and induce Treg cell production in vivo [ 155 ]. Notably, Yasufumi et al reported that human BM-derived MSCs interact with human effector T cells via PD-1/PD-L1 to inhibit CD3z chain and Zap-70 phosphorylation, negatively regulate hexokinase II (HK2) protein expression, and suppress effector T cell glucose metabolism in vitro [ 156 ]. Although the phenotype of effector T cells was not further clarified, this suggests that PD-1/PD-L1 may mediate the immunomodulatory role of MSCs in the metabolic reprogramming of effector T cells.…”

Section: Mesenchymal Stem Cells Regulate the Potential Mechanisms Of ...mentioning

confidence: 99%

Re-establishing immune tolerance in multiple sclerosis: focusing on novel mechanisms of mesenchymal stem cell regulation of Th17/Treg balance

Hu,

Li,

et al. 2024

J Transl Med

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The T-helper 17 (Th17) cell and regulatory T cell (Treg) axis plays a crucial role in the development of multiple sclerosis (MS), which is regarded as an immune imbalance between pro-inflammatory cytokines and the maintenance of immune tolerance. Mesenchymal stem cell (MSC)-mediated therapies have received increasing attention in MS research. In MS and its animal model experimental autoimmune encephalomyelitis, MSC injection was shown to alter the differentiation of CD4+T cells. This alteration occurred by inducing anergy and reduction in the number of Th17 cells, stimulating the polarization of antigen-specific Treg to reverse the imbalance of the Th17/Treg axis, reducing the inflammatory cascade response and demyelination, and restoring an overall state of immune tolerance. In this review, we summarize the mechanisms by which MSCs regulate the balance between Th17 cells and Tregs, including extracellular vesicles, mitochondrial transfer, metabolic reprogramming, and autophagy. We aimed to identify new targets for MS treatment using cellular therapy by analyzing MSC-mediated Th17-to-Treg polarization. Graphical Abstract

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Section: Mesenchymal Stem Cells Regulate the Potential Mechanisms Of ...mentioning

confidence: 99%

Re-establishing immune tolerance in multiple sclerosis: focusing on novel mechanisms of mesenchymal stem cell regulation of Th17/Treg balance

Hu,

Li,

et al. 2024

J Transl Med

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“…The quantity and quality of tumor-killing T cells in the TME are essential for the success of immune therapeutics; however, due to the expression of immune checkpoints, the majority of infiltrating T cells are unable to identify and eliminate neighboring tumor cells ( 70 , 71 ). The PD-1–PD-L1 axis is involved in the BMMSCs-mediated inhibition of T cell glycolysis by negatively regulating HK2 activity ( 72 ). IL-17 can also significantly increase the level of PD-L1 produced by BMMSCs through inducing iNOS expression to shape the immunosuppressive TME ( 73 ).…”

Section: Regulatory Effects Of Mscs From Different Sources On Immune ...mentioning

confidence: 99%

Mesenchymal stem/stromal cells- a principal element for tumour microenvironment heterogeneity

Sun,

Yao

2023

Front. Immunol.

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The heterogeneity of the tumor microenvironment (TME) is a major obstacle in cancer treatment, making most therapeutic interventions palliative rather than curative. Previous studies have suggested that the reason for the low efficacy of immunotherapy and the relapse of the original responders over time may be due to the complex network of mesenchymal stem/stromal cells (MSCs), a population of multipotent progenitor cells existing in a variety of tissues. Cancer-associated MSCs (CA-MSCs) have already been isolated from various types of tumors and are characterized by their vigorous pro-tumorigenic functions. Although the roles of CA-MSCs from different sources vary widely, their origins are still poorly understood. Current evidence suggests that when local resident or distally recruited MSCs interact with tumor cells and other components in the TME, “naïve” MSCs undergo genetic and functional changes to form CA-MSCs. In this review, we mainly focus on the multiple roles of CA-MSCs derived from different sources, which may help in elucidating the formation and function of the entire TME, as well as discover innovative targets for anti-cancer therapies.

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Progression of pre-rheumatoid arthritis to clinical disease of joints: Potential role of mesenchymal stem cells

et al. 2023

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Mesenchymal Stromal Cells Inhibit Aerobic Glycolysis in Activated T Cells by Negatively Regulating Hexokinase II Activity Through PD-1/PD-L1 Interaction

Cited by 4 publications

References 28 publications

Re-establishing immune tolerance in multiple sclerosis: focusing on novel mechanisms of mesenchymal stem cell regulation of Th17/Treg balance

Re-establishing immune tolerance in multiple sclerosis: focusing on novel mechanisms of mesenchymal stem cell regulation of Th17/Treg balance

Mesenchymal stem/stromal cells- a principal element for tumour microenvironment heterogeneity

Progression of pre-rheumatoid arthritis to clinical disease of joints: Potential role of mesenchymal stem cells

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