Functional role of galectin-9 in directing human innate immune reactions to Gram-negative bacteria and T cell apoptosis

Schlichtner, Stephanie; Meyer, N. Helge; Yasinska, Inna M.; Aliu, Nijas; Berger, Steffen; Gibbs, Bernhard F.; Fasler‐Kan, Elizaveta; Sumbayev, Vadim V.

doi:10.1016/j.intimp.2021.108155

Cited by 17 publications

(23 citation statements)

References 30 publications

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“…week 20) and chorion stage (weeks 13–14). In line with our previously reported results ( 3 , 16 ), cells obtained at the chorion stage released significantly higher levels of TGF-β and expressed higher VISTA levels ( Figure 1H ). Also, we reported earlier that Smad3 phosphorylation levels are significantly higher in fetal cells obtained at chorion stage ( 3 ).…”

Section: Resultssupporting

confidence: 93%

“…Firstly, we observed whether TGF-β could induce VISTA expression in human T cells, since this protein was found to mediate galectin-9-induced apoptosis in cytotoxic T lymphocytes ( 9 ). We used non-treated Jurkat T cells (CD4-positive), which express just traces of granzyme B protein ( 9 , 16 ), as well as PMA-activated (activation was performed for 24 h using 100 nM PMA) Jurkat T cells which express granzyme B protein ( 9 , 16 ). Cells were exposed for 24 h to 2 ng/ml TGF-β followed by detection of VISTA expression by Western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, primary human embryonic cells express VISTA protein which is also present on their surface ( 16 ). The earlier the stage of pregnancy, the more TGF-β fetal cells produce ( 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Placental tissues (CVS, chorionic villus sampling) and amniotic fluids were collected after obtaining informed written consent from pregnant women at the University Hospital Bern, Inselspital. Fetal cells were handled and cultured as described before ( 3 , 16 ).…”

Section: Methodsmentioning

confidence: 99%

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Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 – Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

et al. 2022

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Immune checkpoint proteins play crucial roles in human embryonic development but are also used by cancer cells to escape immune surveillance. These proteins and biochemical pathways associated with them form a complex machinery capable of blocking the ability of cytotoxic immune lymphoid cells to attack cancer cells and, ultimately, to fully suppress anti-tumor immunity. One of the more recently discovered immune checkpoint proteins is V-domain Ig-containing suppressor of T cell activation (VISTA), which plays a crucial role in anti-cancer immune evasion pathways. The biochemical mechanisms underlying regulation of VISTA expression remain unknown. Here, we report for the first time that VISTA expression is controlled by the transforming growth factor beta type 1 (TGF-β)-Smad3 signaling pathway. However, in T lymphocytes, we found that VISTA expression was differentially regulated by TGF-β depending on their immune profile. Taken together, our results demonstrate the differential biochemical control of VISTA expression in human T cells and various types of rapidly proliferating cells, including cancer cells, fetal cells and keratinocytes.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 – Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

et al. 2022

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“…Gal-9 has two peptide-linked carbohydrate recognition domains (CRDs), but alternative splicing and proteolytic processing can generate several isoforms [ 109 , 110 ]. Gal-9 has several receptors ( Figure 6 ): the CD44 adhesion molecule [ 111 ], the macrophage marker CD206 (mannose receptor) [ 112 ], the lysosomal associated membrane protein 2 (LAMP2) [ 113 ], the TNF receptor superfamily member CD137 (also known as 4-1BB) [ 114 ], protein disulfide isomerase (PDI) implicated in T cells migration [ 115 , 116 ], the two key immune receptors PD-1 and TIM-3 [ 117 ], bacterial lipopolysaccharides and other proteins equipped with N-glycans [ 109 , 118 ]. Gal-9 has multiple biological functions in cell growth, differentiation, adhesion, communication and death, and is a marker of disease severity [ 119 ].…”

Section: Tim-3/gal-9 Signaling Blockade With α/β-Lactosementioning

confidence: 99%

Modulation of the Gal-9/TIM-3 Immune Checkpoint with α-Lactose. Does Anomery of Lactose Matter?

Bailly

Thuru

Quesnel

2021

Cancers

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The disaccharide lactose is an excipient commonly used in pharmaceutical products. The two anomers, α- and β-lactose (α-L/β-L), differ by the orientation of the C-1 hydroxyl group on the glucose unit. In aqueous solution, a mutarotation process leads to an equilibrium of about 40% α-L and 60% β-L at room temperature. Beyond a pharmaceutical excipient in solid products, α-L has immuno-modulatory effects and functions as a major regulator of TIM-3/Gal-9 immune checkpoint, through direct binding to the β-galactoside-binding lectin galectin-9. The blockade of the co-inhibitory checkpoint TIM-3 expressed on T cells with anti-TIM-3 antibodies represents a promising approach to combat different onco-hematological diseases, in particular myelodysplastic syndromes and acute myeloid leukemia. In parallel, the discovery and development of anti-TIM-3 small molecule ligands is emerging, including peptides, RNA aptamers and a few specifically designed heterocyclic molecules. An alternative option consists of targeting the different ligands of TIM-3, notably Gal-9 recognized by α-lactose. Modulation of the TIM-3/Gal-9 checkpoint can be achieved with both α- and β-lactose. Moreover, lactose is a quasi-pan-galectin ligand, capable of modulating the functions of most of the 16 galectin molecules. The present review provides a complete analysis of the pharmaceutical and galectin-related biological functions of (α/β)-lactose. A focus is made on the capacity of lactose and Gal-9 to modulate both the TIM-3/Gal-9 and PD-1/PD-L1 immune checkpoints in oncology. Modulation of the TIM-3/Gal-9 checkpoint is a promising approach for the treatment of cancers and the role of lactose in this context is discussed. The review highlights the immuno-regulatory functions of lactose, and the benefit of the molecule well beyond its use as a pharmaceutical excipient.

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Biomarkers of early SARS-CoV-2 infection before the onset of respiratory symptoms

Teng,

Quek,

Nguyen

et al. 2024

Clinical Microbiology and Infection

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Functional role of galectin-9 in directing human innate immune reactions to Gram-negative bacteria and T cell apoptosis

Cited by 17 publications

References 30 publications

Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 – Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1 – Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

Modulation of the Gal-9/TIM-3 Immune Checkpoint with α-Lactose. Does Anomery of Lactose Matter?

Biomarkers of early SARS-CoV-2 infection before the onset of respiratory symptoms

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