Tim-1 blockade with RMT1-10 increases T regulatory cells and prolongs the survival of high-risk corneal allografts in mice

Tan, Xiaojun; Jin, Ying; Zhang, Yingnan; Qin, Yi; Xu, Qing; Pan, Zhiqiang

doi:10.1016/j.exer.2014.02.019

Cited by 9 publications

(10 citation statements)

References 30 publications

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“…Tim-1 blockade could prevent immunological rejection and prolong the survival of corneal allograft through regulating T cell responses. 27 As expected, TGF-β1, IL-6, IL-10 and IL-4 were lowly expressed in U87 and U251 cells after Tim-1 knockdown. TGF-β and IL-10 are commonly studied cytokines which have immunosuppressive effects to trigger tumor progression.…”

Section: Discussionsupporting

confidence: 73%

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<p>Knockdown of T Cell Immunoglobulin and Mucin 1 (Tim-1) Suppresses Glioma Progression Through Inhibition of the Cytokine-PI3K/AKT Pathway</p>

Zhou

Fei

Han

et al. 2020

OTT

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Background: Glioma is formed by abnormal proliferation of glial cells in the brain. T cell immunoglobulin and mucin 1 (Tim-1) is linked to cancer development. This study aimed to assess Tim-1 functions in biological behaviors. Methods: The glioma tissues and paracancerous tissues were collected. The pathological morphology of glioma and positive expression of Tim-1 were evaluated. The sh-Tim-1 lentivirus vector was infected into U251 and U87 cells to evaluate glioma cell malignant behaviors. The differentially expressed terms in glioma cells were analyzed by Agilent microarray analysis, and enrichment analyses were performed. Levels of cytokines (TGF-β1, IL-6, IL-4 and IL-10) and the PI3K/AKT pathway were measured. U87 cells with sh-Tim-1 were transplanted into nude mice, and the volume and weight of tumors were measured. Results: Tim-1 levels in glioma tissues and cells were higher than those in glial tissues and cells. Tim-1 knockdown prevented glioma cell proliferation, invasion and migration, and reduced TGF-β1, IL-6, IL-4 and IL-10 levels of glioma. Co-treatment of PI3K/AKT pathway activator and knockdown Tim-1 partially reversed these outcomes. After Tim-1 knockdown, tumor volume and weight and Ki67-positive rate of nude mice were diminished. Conclusion: Tim-1 knockdown inhibited biological behaviors of glioma cells through the PI3K/AKT pathway, which may provide a novel therapy for glioma.

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Section: Discussionsupporting

confidence: 73%

“…Blocking Tim-1 has been reported to inhibit immune rejection. 27 Downregulating TGF-β1 can reduce the invasion ability of glioma cells. 28 Through the bioinformatics website (https://string-db.org/cgi/input.pl?…”

Section: Tim-1 Regulates the Level Of Cytokinesmentioning

confidence: 99%

<p>Knockdown of T Cell Immunoglobulin and Mucin 1 (Tim-1) Suppresses Glioma Progression Through Inhibition of the Cytokine-PI3K/AKT Pathway</p>

Zhou

Fei

Han

et al. 2020

OTT

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“…Blocking the TIM-1-TIM-4 pathway by anti-TIM monoclonal antibody also diminished inflammation and improve apoptosis and survival in renal IRI ( 11 ). The TIM-1-TIM-4 axis is involved in the activation and proliferation of all T cells, including Tregs ( 29 – 32 ), and impacts the infiltration and activation of macrophages and neutrophils as well ( 10 ). Eventually, we found that TIM-1 was elevated in activated T cells after renal IRI, and DZNep treatment significantly downregulated TIM-1 expression.…”

Section: Discussionmentioning

confidence: 99%

Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation

Qiu

et al. 2020

Front. Med.

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Renal ischemia-reperfusion injury (IRI) after renal transplantation often leads to the loss of kidney graft function. However, there is still a lack of efficient regimens to prevent or alleviate renal IRI. Our study focused on the renoprotective effect of 3-Deazaneplanocin A (DZNep), which is a histone methylation inhibitor. We found that DZNep significantly alleviated renal IRI by suppressing nuclear factor kappa-B (NF-κB), thus inhibiting the expression of inflammatory factors in renal tubular epithelial cells in vivo or in vitro. After treatment with DZNep, T cell activation was impaired in the spleen and kidney, which correlated with the downregulated expression of T-cell immunoglobulin mucin (TIM)-1 on T cells and TIM-4 in macrophages. In addition, pretreatment with DZNep was not sufficient to protect the kidney, while administration of DZNep from before to after surgery significantly ameliorated IRI. Our findings suggest that DZNep can be a novel strategy for preventing renal IRI following kidney transplantation.

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“…Anti‐TIM‐1 antibody (Clone RMT1‐10) ameliorates Experimental autoimmune encephalomyelitis (EAE),17 allergic asthma,37 glomerulonephritis38 and corneal allograft rejection 39. In contrast another anti‐TIM‐1 antibody (clone 3B3) enhances T cell proliferation and Th2 effector function 17, 40, 41.…”

Section: Discussionmentioning

confidence: 99%

Anti‐TIM‐1 Monoclonal Antibody (RMT1‐10) Attenuates Atherosclerosis By Expanding IgM‐producing B1a Cells

Hosseini

Kanellakis

et al. 2018

JAHA

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BackgroundPeritoneal B1a cells attenuate atherosclerosis by secreting natural polyclonal immunoglobulin M (IgM). Regulatory B cells expressing T‐cell immunoglobulin mucin domain‐1 (TIM‐1) expanded through TIM‐1 ligation by anti‐TIM‐1 monoclonal antibody (RMT1‐10) induces immune tolerance.Methods and ResultsWe examined the capacity of RMT1‐10 to expand peritoneal B1a cells to prevent atherosclerosis development and retard progression of established atherosclerosis. RMT1‐10 treatment selectively doubled peritoneal B1a cells, tripled TIM‐1+ B1a cells and increased TIM‐1+IgM+interleukin (IL)‐10+ by 3‐fold and TIM‐1+IgM+IL‐10− B1a cells by 2.5‐fold. Similar expansion of B1a B cells was observed in spleens. These effects reduced atherosclerotic lesion size, increased plasma IgM and lesion IgM deposits, and decreased oxidatively modified low‐density lipoproteins in lesions. Lesion CD4+ and CD8+ T cells, macrophages and monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, expression of proinflammatory cytokines monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, IL1β, apoptotic cell numbers and necrotic cores were also reduced. RMT1‐10 treatment failed to expand peritoneal B1a cells and reduce atherosclerosis after splenectomy that reduces B1a cells, indicating that these effects are B1a cell‐dependent. Apolipoprotein E‐KO mice fed a high‐fat diet for 6 weeks before treatment with RMT1‐10 also increased TIM‐1+IgM+ IL‐10+ and TIM‐1+IgM+ IL‐10− B1a cells and IgM levels and attenuated progression of established atherosclerosis.Conclusions RMT1‐10 treatment attenuates atherosclerosis development and progression by selectively expanding IgM producing atheroprotective B1a cells. Antibody‐based in vivo expansion of B1a cells could be an attractive approach for treating atherosclerosis.

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Tim-1 blockade with RMT1-10 increases T regulatory cells and prolongs the survival of high-risk corneal allografts in mice

Cited by 9 publications

References 30 publications

<p>Knockdown of T Cell Immunoglobulin and Mucin 1 (Tim-1) Suppresses Glioma Progression Through Inhibition of the Cytokine-PI3K/AKT Pathway</p>

<p>Knockdown of T Cell Immunoglobulin and Mucin 1 (Tim-1) Suppresses Glioma Progression Through Inhibition of the Cytokine-PI3K/AKT Pathway</p>

Histone Methylation Inhibitor DZNep Ameliorated the Renal Ischemia-Reperfusion Injury via Inhibiting TIM-1 Mediated T Cell Activation

Anti‐TIM‐1 Monoclonal Antibody (RMT1‐10) Attenuates Atherosclerosis By Expanding IgM‐producing B1a Cells

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