Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)–1/TIM4 interaction as a therapeutic strategy in a dendritic cell–induced peanut allergy model

Feng, Bai–Sui; Chen, Xiao; He, Shaoheng; Zheng, Peng‐Yuan; Foster, J.R.; Xing, Zhou; Bienenstock, John; Yang, Ping‐Chang

doi:10.1016/j.jaci.2008.04.036

Cited by 94 publications

(112 citation statements)

References 23 publications

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“…In naive T cells, Tim-4 negatively regulates activation via a ligand other than Tim-1, while Tim-4 positively regulates activation through Tim-1 in pre-activated T cells. 41 Emerging reports show that DCderived Tim-4 plays an important role in the initiation of peanut extract-specific Th2 polarization and allergy in the intestine, 42 which may explain our result that Tim-4 is positively correlated with Tim-1 in SLE patients but not in healthy controls. In SLE patients, cells overexpressing Tim-4 might bind to pre-activated Tim-1-bearing T cells, especially Th2 cells, and promote Th2-mediated immune responses, consistent with the idea that SLE is Th2-polarized autoimmune disease.…”

Section: Discussionmentioning

confidence: 54%

Increased expression of human T-cell immunoglobulin- and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus

Zhao

Wang³

et al. 2010

Cell Mol Immunol

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Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease. Innate and adaptive immunity cooperatively contribute to the development of SLE. Antigen-presenting cells (APCs) have been suggested to link innate and adaptive immunity. T-cell immunoglobulin-and mucin-domain-containing molecule-4 (Tim-4; also known as Timd4), expressed primarily on the surface of APCs, is a member of the TIM family, a recently described group of molecules that have received much attention as potential regulators of the immune system. In this study, we used quantitative real-time reverse transcription-polymerase chain reaction to examine the mRNA expression of Tim-4 in peripheral blood mononuclear cells (PBMCs) from SLE patients and further analyzed the correlation between the expression of Tim-4 and Tim-1 (a potential ligand for Tim-4) in PBMCs and serum tumor necrosis factor (TNF)-a levels. The results showed that Tim-4 mRNA expression in PBMCs was significantly higher in SLE patients than in healthy controls, especially those patients in the active phase of disease. Moreover, Tim-4 mRNA levels were closely correlated with Tim-1 mRNA levels in PBMCs and with serum TNF-a levels in SLE patients but not in the control group. Taken together, these results demonstrate that Tim-4 may be involved in the pathogenesis of SLE.

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Section: Discussionmentioning

confidence: 54%

Increased expression of human T-cell immunoglobulin- and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus

Zhao

Wang³

et al. 2010

Cell Mol Immunol

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“…LPS treatment stimulated TIM-3 expression in HBE cells and particularly increased TIM-3 levels in CFBE cells. In addition, TIM receptor expression has been shown to be modulated by other bacterial toxins, for instance, TIM-4, which has been reported to be upregulated by Staphylococcal enterotoxin B (55) and cholera toxin (56). Interestingly, LPS treatment downregulated TIM-3 expression in dendritic cells (57), whereas LPS exposure upregulated TIM-3 expression in endothelial cells (28), indicating a cell-type-specific response.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of TIM-3–Galectin-9 Pathway in the Cystic Fibrosis Airways

Vega-Carrascal

Reeves

Niki

et al. 2011

The Journal of Immunology

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The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inflammatory conditions. It has been reported that proinflammatory cytokine dysregulation and neutrophil-dominated inflammation are the main causes of morbidity in cystic fibrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways.

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“…The spleen and small intestine were excised. Following our established procedures (14,15), spleen cells and lamina propria mononuclear cells (LPMCs) were isolated for use in further experiments.…”

Section: Methodsmentioning

confidence: 99%

Insulin-like Growth Factor-2 Enhances Functions of Antigen (Ag)-specific Regulatory B Cells

Geng¹,

Yang²,

Li³

et al. 2014

Journal of Biological Chemistry

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Disruption of T-cell immunoglobulin and mucin domain molecule (TIM)–1/TIM4 interaction as a therapeutic strategy in a dendritic cell–induced peanut allergy model

Cited by 94 publications

References 23 publications

Increased expression of human T-cell immunoglobulin- and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus

Increased expression of human T-cell immunoglobulin- and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus

Dysregulation of TIM-3–Galectin-9 Pathway in the Cystic Fibrosis Airways

Insulin-like Growth Factor-2 Enhances Functions of Antigen (Ag)-specific Regulatory B Cells

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