Activated Galectin‐9/Tim3 promotes Treg and suppresses Th1 effector function in chronic lymphocytic leukemia

Pang, Nannan; Alimu, Xierenguli; Chen, Rong; Muhashi, Maliya; Ma, Jiajia; Chen, Gang; Zhao, Fang; Wang, Lei; Qu, Jianhua; Ding, Jianbing

doi:10.1096/fj.202100013r

Cited by 36 publications

(37 citation statements)

References 35 publications

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“…Here, we selectively isolated human naive CD4 + T cells and treated them with Gal-9, to assess the ability of Gal-9 to drive human T cell differentiation. In line with previous studies (49,50), we found that Gal-9 alone was effective at inducing Treg differentiation in a dose-dependent manner. Moreover, there was also a dose-dependent increase in IL-10 levels in supernatants from Gal-9 treated T cell cultures, suggesting a specific role for Gal-9 in inducing Treg functions (i.e., IL-10 production).…”

Section: Discussionsupporting

confidence: 92%

Galectin-9 Regulates Monosodium Urate Crystal-Induced Gouty Inflammation Through the Modulation of Treg/Th17 Ratio

et al. 2021

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Gout is caused by depositing monosodium urate (MSU) crystals within the articular area. The infiltration of neutrophils and monocytes drives the initial inflammatory response followed by lymphocytes. Interestingly, emerging evidence supports the view that in situ imbalance of T helper 17 cells (Th17)/regulatory T cells (Treg) impacts the subsequent damage to target tissues. Galectin-9 (Gal-9) is a modulator of innate and adaptive immunity with both pro- and anti-inflammatory functions, dependent upon its expression and cellular location. However, the specific cellular and molecular mechanisms by which Gal-9 modulates the inflammatory response in the onset and progression of gouty arthritis has yet to be elucidated. In this study, we sought to comprehensively characterise the functional role of exogenous Gal-9 in an in vivo model of MSU crystal-induced gouty inflammation by monitoring in situ neutrophils, monocytes and Th17/Treg recruited phenotypes and related cyto-chemokines profile. Treatment with Gal-9 revealed a dose-dependent reduction in joint inflammation scores, knee joint oedema and expression of different pro-inflammatory cyto-chemokines. Furthermore, flow cytometry analysis highlighted a significant modulation of infiltrating inflammatory monocytes (CD11b+/CD115+/LY6-Chi) and Th17 (CD4+/IL-17+)/Treg (CD4+/CD25+/FOXP-3+) cells following Gal-9 treatment. Collectively the results presented in this study indicate that the administration of Gal-9 could provide a new therapeutic strategy for preventing tissue damage in gouty arthritic inflammation and, possibly, in other inflammatory-based diseases.

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Section: Discussionsupporting

confidence: 92%

Galectin-9 Regulates Monosodium Urate Crystal-Induced Gouty Inflammation Through the Modulation of Treg/Th17 Ratio

et al. 2021

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“…Therefore, in aortic aneurysms, MIF from T cells plays a role in promoting the transformation of VSMCs to macrophage-like VSMCs, while MIF from VSMCs recruits immune cells (especially B cells) into aortic aneurysms. As previous studies showed that galectin 9–CD44 interaction is in favor of stability and function of adaptive regulatory T cells ( 29 ), galectin 9–CD45 inhibits naive B-cell activation ( 30 ), and can inhibit CD4 + T-cell expansion and suppress Th1 effector function ( 31 ). Hence, we speculate that macrophage-like VSMCs and macrophages both exert an immunomodulatory capacity through the galectin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data

Cao

Zhengchao

et al. 2022

Front. Cardiovasc. Med.

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BackgroundVascular smooth muscle cell (VSMC) phenotype switching has been preliminarily found in aortic aneurysms. However, two major questions were raised: (1) What factors drive phenotypic switching of VSMCs in aortic aneurysms? (2) What role does VSMC phenotype transformation play in aortic aneurysms? We speculated that the interaction between infiltrated immune cells and VSMCs played a pivotal role in aortic aneurysm expansion.Materials and MethodsWe obtained single-cell transcriptome data GSE155468 that incorporate eight aortic aneurysm samples and three normal aorta samples. A standard single-cell analysis procedure was performed by Seurat (v3.1.2) for identifying the general cell components. Subsequently, VSMCs were extracted separately and re-clustered for identifying switched VSMC phenotypes. VSMC phenotype annotation was relied on the definitions of specific VSMC phenotypes in published articles. Vital VSMC phenotypes were validated by immunofluorescence. Next, identified immune cells and annotated vital VSMC phenotypes were extracted for analyzing the intercellular communication. R package CellChat (v1.1.3) was used for investigating the communication strength, signaling pathways, and communication patterns between various VSMC phenotypes and immune cells.ResultA total of 42,611 cells were identified as CD4 + T cells, CD8 + T cells, VSMC, monocytes, macrophages, fibroblasts, endothelial cells, and B cells. VSMCs were further classified into contractile VSMCs, secreting VSMCs, macrophage-like VSMCs, mesenchymal-like VSMCs, adipocyte-like VSMCs, and T-cell-like VSMCs. Intercellular communication analysis was performed between immune cells (macrophages, B cells, CD4 + T cells, CD8 + T cells) and immune related VSMCs (macrophage-like VSMCs, mesenchymal-like VSMCs, T-cell-like VSMCs, contractile VSMCs). Among selected cell populations, 27 significant signaling pathways with 61 ligand–receptor pairs were identified. Macrophages and macrophage-like VSMCs both assume the roles of a signaling sender and receiver, showing the highest communication capability. T cells acted more as senders, while B cells acted as receivers in the communication network. T-cell-like VSMCs and contractile VSMCs were used as senders, while mesenchymal-like VSMCs played a poor role in the communication network. Signaling macrophage migration inhibitory factor (MIF), galectin, and C-X-C motif chemokine ligand (CXCL) showed high information flow of intercellular communication, while signaling complement and chemerin were completely turned on in aortic aneurysms. MIF and galectin promoted VSMC switch into macrophage-like phenotypes, CXCL, and galectin promoted VSMCs transform into T-cell-like phenotypes. MIF, galectin, CXCL, complement, and chemerin all mediated the migration and recruitment of immune cells into aortic aneurysms.ConclusionThe sophisticated intercellular communication network existed between immune cells and immune-related VSMCs and changed as the aortic aneurysm progressed. Signaling MIF, galectin, CXCL, chemerin, and complement made a significant contribution to aortic aneurysm progression through activating immune cells and promoting immune cell migration, which could serve as the potential target for the treatment of aortic aneurysms.

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“…Tregs further inhibit CD4 + T H cell proliferation and function by secreting cytokines such as IL-10 and inhibiting IL-2 availability for CD4 + T H cells (34,35). The balance between T H 1 and Treg cells has drawn great attention in cancer (36), various inflammatory diseases (37,38), and autoimmunity diseases (39). Treg accumulation and T H 1 cell downregulation are also necessary for the convalescence of crescentic glomerulonephritis (40).…”

Section: Discussionmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis

Qiu¹,

Cao²,

Tu³

et al. 2021

Front. Immunol.

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BackgroundRenal fibrosis is inevitable in all progressive chronic kidney diseases (CKDs) and represents a serious public health problem. Immune factors contribute to the progression of renal fibrosis. Thus, it is very possible that immunosuppression cells, such as myeloid-derived suppressor cells (MDSCs), could bring benefits to renal fibrosis. Herein, this study investigated the antifibrotic and reno-protective effect of MDSCs and the possible mechanisms.MethodsMurine and cell models of unilateral ureter obstruction (UUO) renal fibrosis were used. Bone marrow-induced MDSCs and granulocyte–macrophage colony-stimulating factor (GM-CSF) were pretreated before surgery. Kidney weight, pathological injury, extracellular matrix deposition, and epithelial–mesenchymal transition progression were examined. Transforming growth factor (TGF)-β1)/Smad/Snail signaling pathway involvement was investigated through Western blotting and quantitative PCR (qPCR). Accumulation of MDSC, CD4+ T cell, regulatory T (Treg), and T helper 1 (TH1) cell accumulation, and CCL5 and CCR5 expression level in MDSCs and non-MDSCs were evaluated using flow cytometry.ResultsIn vitro- and in vivo-induced MDSCs significantly ameliorated UUO-induced tubulointerstitial fibrosis, inhibited the TGF-β1/Smad/Snail signaling pathway, and enhanced MDSC and Treg infiltration in the kidney while downregulating the TH1 cells. Both in vitro and in vivo experiments confirmed CCL5 elevation in the two MDSC-treated groups.ConclusionIn vitro- and in vivo-induced MDSCs alleviated renal fibrosis similarly through promoting the CCL5–CCR5 axis interaction and TGF-β1/Smad/Snail signaling pathway inhibition. Our results indicate an alternative treatment for renal fibrosis.

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Activated Galectin‐9/Tim3 promotes Treg and suppresses Th1 effector function in chronic lymphocytic leukemia

Cited by 36 publications

References 35 publications

Galectin-9 Regulates Monosodium Urate Crystal-Induced Gouty Inflammation Through the Modulation of Treg/Th17 Ratio

Galectin-9 Regulates Monosodium Urate Crystal-Induced Gouty Inflammation Through the Modulation of Treg/Th17 Ratio

Deciphering the Intercellular Communication Between Immune Cells and Altered Vascular Smooth Muscle Cell Phenotypes in Aortic Aneurysm From Single-Cell Transcriptome Data

Myeloid-Derived Suppressor Cells Alleviate Renal Fibrosis Progression via Regulation of CCL5-CCR5 Axis

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