Mannose Metabolism Is Essential for Th1 Cell Differentiation and IFN-γ Production

Zygmunt, Beata M.; Węgrzyn, Agnieszka; Gajska, Weronika; Yevsa, Tetyana; Chodaczek, Grzegorz; Guzmán, Carlos A.

doi:10.4049/jimmunol.1700042

Cited by 7 publications

(6 citation statements)

References 47 publications

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“…Stimulation with IL-15 enhanced glycolysis in murine CD8 memory T cells 47 and in the TEMRA CD8 T cells from HVs or immune-challenged patients (KTs), 20 and 2-DG, an inhibitor of glycolysis, efficiently prevents the IL-15–induced activation of TEMRA CD8 T cells 20 . In addition to inhibition of glycolysis, 2-DG could directly alter protein glycosylation in natural killer (NK) cells, 48 and mannose metabolism was essential for CD4 T1H differentiation 49 . We thus hypothesized that the selective targeting of glycolysis could prevent not only CD8 T cell activation but also migration by limiting sialic acid biosynthesis and the transition to a functional conformation of PSGL1.…”

Section: Resultsmentioning

confidence: 99%

Effector Memory–Expressing CD45RA (TEMRA) CD8+ T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor–Dependent Proinflammatory and Migratory Responses

Ngoc

Tilly

Danger

et al. 2022

JASN

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BackgroundThe mechanisms regulating CD8+T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8+T cells that re-express CD45RA (TEMRA CD8+T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection.MethodsWe used single-cell proteomic profiling and functional testing of CD8+T cell subsets to characterize their effector functions and migratory properties in healthy volunteers and kidney transplant recipients with stable or humoral rejection.ResultsWe showed that humoral rejection of a kidney allograft is associated with an accumulation of cytolytic TEMRA CD8+T cells in blood and kidney graft biopsies. TEMRA CD8+T cells from kidney transplant recipients exhibited enhanced migratory properties compared with effector memory (EM) CD8+T cells, with enhanced adhesion to activated endothelium and transmigration in response to the chemokine CXCL12. CXCL12 directly triggers a purinergic P2×4 receptor–dependent proinflammatory response of TEMRA CD8+T cells from transplant recipients. The stimulation with IL-15 promotes the CXCL12-induced migration of TEMRA and EM CD8+T cells and promotes the generation of functional PSGL1, which interacts with the cell adhesion molecule P-selectin and adhesion of these cells to activated endothelium. Although disruption of the interaction between functional PSGL1 and P-selectin prevents the adhesion and transmigration of both TEMRA and EM CD8+T cells, targeting VLA-4 or LFA-1 (integrins involved in T cell migration) specifically inhibited the migration of TEMRA CD8+T cells from kidney transplant recipients.ConclusionsOur findings highlight the active role of TEMRA CD8+T cells in humoral transplant rejection and suggest that kidney transplant recipients may benefit from therapeutics targeting these cells.

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Section: Resultsmentioning

confidence: 99%

Effector Memory–Expressing CD45RA (TEMRA) CD8+ T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor–Dependent Proinflammatory and Migratory Responses

Ngoc

Tilly

Danger

et al. 2022

JASN

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“…Supplementation with mannose could partially restore IFNγ production in cells cultured with the glycolysis inhibitor 2-deoxy-D-glucose (2DG). Interestingly, the transcription factor T-bet, which is crucial for Th1 differentiation, was reduced when cells were cultured in the presence of galactose, but was restored by mannose supplementation ( 114 ). Lastly, inhibition of GLS-1 has been shown to increase Th1 differentiation ( 73 ).…”

Section: T Cell Metabolism: From Quiescence To Effector Functionmentioning

confidence: 99%

T Cell Metabolism in Infection

Wik

Skålhegg

2022

Front. Immunol.

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T lymphocytes (T cells) are divided into two functionally different subgroups the CD4+ T helper cells (Th) and the CD8+ cytotoxic T lymphocytes (CTL). Adequate CD4 and CD8 T cell activation to proliferation, clonal expansion and effector function is crucial for efficient clearance of infection by pathogens. Failure to do so may lead to T cell exhaustion. Upon activation by antigen presenting cells, T cells undergo metabolic reprograming that support effector functions. In this review we will discuss how metabolic reprograming dictates functionality during viral infections using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) as examples. Moreover, we will briefly discuss T cell metabolic programs during bacterial infections exemplified by Mycobacterium tuberculosis (MT) infection.

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“…Inhibiting glycolysis by administering 2-DG results in the loss of Th1 cell differentiation and IFN-γ production (Shi et al, 2011) Another study has revealed that glycolytic metabolite phosphoenolpyruvate is necessary for calcium signaling which in turn promotes Th1 cell differentiation and proliferation (Ho et al, 2015). Mannose metabolism is also one of the most important regulators of Th1 cell differentiation (Zygmunt et al, 2018). A study in lung cancer unveiled that presence of T cell-intrinsic oxygen-sensing marker prolyl hydroxylase (PHD) not only prevents Th1 cell activity but also promotes Treg functionality (Clever et al, 2016).…”

Section: Th1 Cellsmentioning

confidence: 99%

Regulation of immune cell metabolism in health and disease: Special focus on T and B cell subsets

Chakraborty

Khamaru

Bhattacharyya

2022

Cell Biology International

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Metabolism is a dynamic process and keeps changing from time to time according to the demand of a particular cell to meet its bio‐energetic requirement. Different immune cells rely on distinct metabolic programs which allow the cell to balance its requirements for energy, molecular biosynthesis, and effector activity. In the aspect of infection and cancer immunology, effector T and B cells get exhausted and help tumor cells to evade immunosurveillance. On the other hand, T cells become hyperresponsive in the scenario of autoimmune diseases. In this article, we have explored the uniqueness and distinct metabolic features of key CD4+ T and B helper cell subsets, CD4+ T, B regulatory cell subsets and CD8+ T cells regarding health and disease. Th1 cells rely on glycolysis and glutaminolysis; inhibition of these metabolic pathways promotes Th1 cells in Treg population. However, Th2 cells are also dependent on glycolysis but an abundance of lactate within TME shifts their metabolic dependency to fatty acid metabolism. Th17 cells depend on HIF‐1α mediated glycolysis, ablation of HIF‐1α reduces Th17 cells but enhance Treg population. In contrast to effector T cells which are largely dependent on glycolysis for their differentiation and function, Treg cells mainly rely on FAO for their function. Therefore, it is of utmost importance to understand the metabolic fates of immune cells and how it facilitates their differentiation and function for different disease models. Targeting metabolic pathways to restore the functionality of immune cells in diseased conditions can lead to potent therapeutic measures.

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Mannose Metabolism Is Essential for Th1 Cell Differentiation and IFN-γ Production

Cited by 7 publications

References 47 publications

Effector Memory–Expressing CD45RA (TEMRA) CD8+ T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor–Dependent Proinflammatory and Migratory Responses

Effector Memory–Expressing CD45RA (TEMRA) CD8+ T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor–Dependent Proinflammatory and Migratory Responses

T Cell Metabolism in Infection

Regulation of immune cell metabolism in health and disease: Special focus on T and B cell subsets

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