Soluble Form of T Cell Ig Mucin 3 Is an Inhibitory Molecule in T Cell-Mediated Immune Response

Geng, Hui; Zhang, Guimei; Liu, Dong; Zhang, Hui; Yuan, Ye; Zhu, Haifeng; Xiao, Han; Han, Lu; Feng, Zuo-Hua

doi:10.4049/jimmunol.176.3.1411

Cited by 113 publications

(94 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously showed that Tim-3 may act as a signal molecule to promote tumor progression (18). Here, we further provide evidence that Tim-3 expression in endothelial cells in tumor and lung could be induced by the TLR4 ligand.…”

Section: Discussionsupporting

confidence: 53%

See 1 more Smart Citation

Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-κB pathway

Yuan²,

Liu³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

Abstract. T cell immunoglobulin and mucin domain-3 (Tim-3)is originally recognized as a receptor of Th1 cells. We found that Tim-3 could be expressed in endothelial cells after stimulation with tumor cell-released TLR4 ligand. Tim-3 expressed by endothelial cells does not function as the receptor of galectin-9, but mediates the interaction of endothelial cells with tumor cells. The engagement of endothelial cellexpressed Tim-3 with a non-galectin 9 putative receptor on B16 melanoma cells could trigger the NF-κB signaling pathway in B16 cells. The activated NF-κB not only promoted the proliferation of B16 cells, but also enhanced apoptosis resistance of B16 cells by up-regulating Bcl-2 and Bcl-xL and down-regulating Bax. Consistently, Tim-3 facilitated the survival of B16 cells in the blood stream, arrested in the lung and following invasion, resulted in more metastatic nodules in the lung. These findings suggest that endothelial cell-expressed Tim-3 increases tumor cell metastatic potential by facilitating tumor cell intravasation, survival in blood stream and extravasation. Thus, antiinflammation or blockade of Tim-3 may contribute to the prevention of metastasis.

show abstract

Section: Discussionsupporting

confidence: 53%

“…Eukaryotic expression vector pTim-3 carrying the cDNA encoding full-length mouse Tim-3 was preserved in the laboratory (18). CHO cells were transfected with pTim-3 or pcDNA3.1 with FuGene 6 transfection reagent (Roche, Indianapolis, IN) according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-κB pathway

Yuan²,

Liu³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…The administration of galectin-9 results in a selective reduction of IFN-␥ producing cells and suppression of Th1-mediated autoimmune encephalomyelitis in vivo (13). Soluble form of Tim-3 inhibits Agspecific T cell responses in vitro and reduced antitumor immunity in vivo by inhibiting effector Th1 responses (14). Overall, these data suggest that the Tim-3-Tim-3L pathway may contribute to the attenuation of Th1-mediated responses.…”

Section: Cd25mentioning

confidence: 64%

Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease

Oikawa

Kamimura

Akiba

et al. 2006

The Journal of Immunology

102

View full text Add to dashboard Cite

Tim-3, a member of the T cell Ig mucin (TIM) family regulates effector Th1 responses. We examined Tim-3 and its ligand expression as well as the effects of anti-Tim-3 mAb treatment in a murine model of acute graft-vs-host disease (aGVHD). In mice with aGVHD, Tim-3 expression was markedly up-regulated on splenic and hepatic CD4+ and CD8+ T cells, dendritic cells (DCs), and macrophages, and this was especially dramatic in hepatic CD8+ T cells. Both donor- and host-derived CD8+ T cells induced similar levels of Tim-3. Tim-3 ligand expression was also up-regulated in splenic T cells, DCs, and macrophages, but not in the hepatic lymphocytes. The administration of anti-Tim-3 mAbs accelerated aGVHD, as demonstrated by body weight loss, reduction in total splenocyte number, and infiltration of lymphocytes in the liver. IFN-γ expression by splenic and hepatic CD4+ and CD8+ T cells was significantly augmented by anti-Tim-3 mAb treatment. In addition, the cytotoxicity against host alloantigen by donor CD8+ T cells was enhanced. These results demonstrate that the anti-Tim-3 treatment in aGVHD augmented the activation of effector T cells expressing IFN-γ or exerting cytotoxicity. Our results suggest that Tim-3 may play a crucial role in the regulation of CD8+ T cells responsible for the maintenance of hepatic homeostasis and tolerance.

show abstract

“…Plasmids were prepared and analyzed as described previously (27). Mice received the injection of plasmid DNA (in 100 ml saline) into the muscle tissue (i.m.…”

Section: In Vivo Gene Transfectionmentioning

confidence: 99%

IL-6 Cooperates with G-CSF To Induce Protumor Function of Neutrophils in Bone Marrow by Enhancing STAT3 Activation

Yan

Wei

Yuan

et al. 2013

The Journal of Immunology

Self Cite

112

View full text Add to dashboard Cite

Neutrophils are known to have antitumor potential. However, in recent years the tumor-promoting effect of neutrophils has been well demonstrated. So far, it remains unclear what causes the conversion of neutrophil function from tumor suppressive to tumor promoting. In this article, we report that the conversion of murine neutrophil function occurs in bone marrow, and that IL-6 cooperation with G-CSF is required for this conversion. IL-6 cooperated with G-CSF to modulate neutrophils in bone marrow, altering the activation potential of signaling pathways in neutrophils, especially that of STAT3. Costimulation with G-CSF and IL-6 induced a higher level of phospho-STAT3 in neutrophils, which was further increased by upregulation of STAT3 expression in neutrophils owing to downregulation of IFN-β expression in bone marrow macrophages by IL-6. Augmented STAT3 activation was crucial for upregulating the expression of Mmp9 and Bv8 genes and downregulating the expression of Trail and Rab27a genes in neutrophils. Moreover, G-CSF/IL-6–modulated neutrophils could not efficiently release azurophilic granules because of downregulation of Rab27a and inefficient activation of PI3K and p38 MAPK pathways. Because of premodulation by G-CSF and IL-6, neutrophils in response to complex stimuli in tumor released much less myeloperoxidase, neutrophil elastase, and TRAIL, but showed much higher expression of Mmp9 and Bv8 genes. Taken together, these results demonstrate that G-CSF and IL-6, despite their well-known physiological functions, could modulate the activation potential of signaling pathways in neutrophils, resulting in the production or release of the above-mentioned factors in a way that favors tumor angiogenesis and tumor growth.

show abstract

Soluble Form of T Cell Ig Mucin 3 Is an Inhibitory Molecule in T Cell-Mediated Immune Response

Cited by 113 publications

References 36 publications

Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-κB pathway

Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-κB pathway

Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease

IL-6 Cooperates with G-CSF To Induce Protumor Function of Neutrophils in Bone Marrow by Enhancing STAT3 Activation

Contact Info

Product

Resources

About