CD147 participates in the activation function of circulating angiogenic T cells in patients with rheumatoid arthritis

Zhao, Peng; Miao, Jinlin; Zhang, Kui; Zi, Yu; Lv, Miaomiao; Xu, Ying-Ming; Fu, Xianghui; Han, Qin; Zhu, Ping

doi:10.1007/s10067-019-04584-4

Cited by 10 publications

(9 citation statements)

References 26 publications

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“…21 In contrast to many other studies of novel RA drug delivery systems, which focus on potentiating anti-inflammatory and analgesic effects, we also examined the ability of our system to inhibit angiogenesis because new blood vessel formation, synovial hyperplasia, and inflammatory cell infiltration in RA support pannus growth and disease progression. 1 We assayed for antiangiogenic effects using the CAM assay, which is normally utilized to investigate tumor angiogenesis. 26 The angiogenesis in RA is similar to that in tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Rheumatoid arthritis (RA) as a chronic autoimmune disease includes inflammatory and angiogenic processes . Lack of cure for RA reflects its multifactorial, complex etiology. , RA is associated with the infiltration of inflammatory mononuclear cells, excessive synovial hyperplasia, pannus formation over the joint surface, and progressive joint destruction .…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Rheumatoid Arthritis by Serum Albumin Nanoparticles Coated with Mannose to Target Neutrophils

Lyu

Wang

Bai

et al. 2020

ACS Appl. Mater. Interfaces

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Rheumatoid arthritis (RA) is an angiogenic and chronic inflammatory disease. One of the most extensively used first-line drugs against RA is methotrexate (MTX), but it shows poor solubility, short in vivo circulation, and off-target binding, leading to strong toxicity. To overcome these shortcomings, the present study loaded MTX into nanoparticles of human serum albumin modified with mannose (MTX-M-NPs) to target the drug to neutrophils. MTX-M-NPs were prepared, and their uptake by neutrophils was studied using laser confocal microscopy and flow cytometry. A chick chorioallantoic membrane assay was used to assess their ability to inhibit angiogenesis. The pharmacokinetics and tissue distribution of MTX-M-NPs were investigated using fluorescence microscopy and high-performance liquid chromatography. Their pharmacodynamics was evaluated in a rat model with arthritis induced by collagen. Neutrophils took up MTX-M-NPs significantly better than the same nanoparticles (NPs) without mannose. MTX-M-NPs markedly suppressed angiogenesis in chick embryos, and the MTX circulation was significantly longer when it was delivered as MTX-M-NPs than as a free drug. MTX-M-NPs accumulated mainly in arthritic joints. The retention of NPs was promoted by mannose-derived coating in arthritic joints. Serum levels of inflammatory cytokines, joint swelling, and bone erosion were significantly decreased by MTX-M-NPs. In conclusion, these NPs can prolong the in vivo circulation of MTX and target it to the sites of inflammation in RA, reducing drug toxicity. MTX-M-NPs allow the drug to exert its intrinsic anti-inflammatory, antiangiogenic, and analgesic properties, making it a useful drug delivery system in RA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment of Rheumatoid Arthritis by Serum Albumin Nanoparticles Coated with Mannose to Target Neutrophils

Lyu

Wang

Bai

et al. 2020

ACS Appl. Mater. Interfaces

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“…Gal-9 is also expressed in vascular endothelial cells with several functions, including modulating the phosphorylation of VEGF-receptor3 and insulin-like growth factor 1, regulating the RTK pathway, mediating the adhesion between tumoral and endothelial cells, regulating the proliferation and metastasis of tumor cells [31,32]. Rodriguez-Carrio J et al reported reduced numbers of angiogenic T cells and endothelial progenitor cells in RA patients [33], but another study found an elevated percentage of circulating angiogenic T cells that positively correlated with the percentage of endothelial progenitor cells in RA patients, which regulated VEGF levels through Akt signaling with CD147 [34]. Our previous cross-sectional study on Gal-9 level in 105 RA patients have included the same baseline data of some RA patients in this prospective cohort [15].…”

Section: Discussionmentioning

confidence: 99%

Galectin-9 expression correlates with efficacy of tacrolimus therapy in rheumatoid arthritis

Shu

Sun

Sui

et al. 2020

Preprint

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Background: The calcineurin inhibitor tacrolimus (TAC) is the second-line treatment for rheumatoid arthritis (RA). Galectin-9 (Gal-9) is a multifunctional immunomodulatory factor highly expressed in RA synovial tissues and synovial fluid. This study aimed to investigate the expression of Gal-9 and its correlation with disease activity and response to TAC in RA patients.Methods: Active RA patients were enrolled and treated with TAC alone or in combination with methotrexate and/or prednisone for 12 weeks in a prospective cohort study. Clinical and immunological parameters were recorded at baseline and at week 12. We measured Gal-9 expression in different subsets of peripheral blood mononuclear cells using flow cytometry and assayed Gal-9 levels in plasma. We also tested cytokine levels in plasma by ELISA. Results: The disease activity of RA patients notably decreased after TAC treatment. At baseline, the percentages of CD4+ T cells and T regulatory cells (CD4+CD25+CD127low) expressing Gal-9 were higher in the group with severe disease than in mild or moderate groups. After TAC treatment in RA patients, the Gal-9 expression in CD3+, CD4+, CD8+ and CD4-CD8- cell subsets decreased, as well as Gal-9 mean fluorescence intensity in CD3+, CD4+ and CD8+ T cells. Similarly, plasma Gal-9 levels were lower at week 12 than at baseline. Good responders showed significantly lower Gal-9 expression on CD3+ and CD4+ T cell subsets as well as lower plasma Gal-9 levels than poor responders. Gal-9 expression positively correlates with disease activity in RA patients.Conclusion: Gal-9 can be regarded as a new biomarker for evaluating RA activity and efficacy of TAC.

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“…Some authors suggest that Tang cells might be a novel T cell related to glandular neo-angiogenesis and inflammation leading to endothelial dysfunction observed as extraglandular manifestations in pSS patients. Even though more evidence is necessary to reinforce Tang cell pathologic roles in SS, these cells have been widely associated with endothelial dysfunction in other autoimmune disease [ 115 , 118 , 119 ].…”

Section: Emerging T Cellsmentioning

confidence: 99%

T Cells Subsets in the Immunopathology and Treatment of Sjogren’s Syndrome

2020

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Sjogren’s syndrome (SS) is an autoimmune disease whose pathogenesis is characterized by an exacerbated T cell infiltration in exocrine glands, markedly associated to the inflammatory and detrimental features as well as the disease progression. Several helper T cell subsets sequentially converge at different stages of the ailment, becoming involved in specific pathologic roles. Initially, their activated phenotype endows them with high migratory properties and increased pro-inflammatory cytokine secretion in target tissues. Later, the accumulation of immunomodulatory T cells-derived factors, such as IL-17, IFN-γ, or IL-21, preserve the inflammatory environment. These effects favor strong B cell activation, instigating an extrafollicular antibody response in ectopic lymphoid structures mediated by T follicular helper cells (Tfh) and leading to disease progression. Additionally, the memory effector phenotype of CD8+ T cells present in SS patients suggests that the presence of auto-antigen restricted CD8+ T cells might trigger time-dependent and specific immune responses. Regarding the protective roles of traditional regulatory T cells (Treg), uncertain evidence shows decrease or invariable numbers of circulating and infiltrating cells. Nevertheless, an emerging Treg subset named follicular regulatory T cells (Tfr) seems to play a critical protective role owing to their deficiency that enhances SS development. In this review, the authors summarize the current knowledge of T cells subsets contribution to the SS immunopathology, focusing on the cellular and biomolecular properties allowing them to infiltrate and to harm target tissues, and that simultaneously make them key therapeutic targets for SS treatment.

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CD147 participates in the activation function of circulating angiogenic T cells in patients with rheumatoid arthritis

Cited by 10 publications

References 26 publications

Treatment of Rheumatoid Arthritis by Serum Albumin Nanoparticles Coated with Mannose to Target Neutrophils

Treatment of Rheumatoid Arthritis by Serum Albumin Nanoparticles Coated with Mannose to Target Neutrophils

Galectin-9 expression correlates with efficacy of tacrolimus therapy in rheumatoid arthritis

T Cells Subsets in the Immunopathology and Treatment of Sjogren’s Syndrome

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