Vav1-phospholipase C-γ1 (Vav1-PLC-γ1) Pathway Initiated by T Cell Antigen Receptor (TCRγδ) Activation Is Required to Overcome Inhibition by Ubiquitin Ligase Cbl-b during γδT Cell Cytotoxicity

Yin, Shanshan; Zhang, Jianmin; Mao, Yujia; Hu, Yu; Cui, Lianxian; Kang, Ning; Wang, He

doi:10.1074/jbc.m113.484600

Cited by 20 publications

(17 citation statements)

References 54 publications

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“…TSPO expression of different tissues was examined by Western blot as previously described[19]. Tissues were homogenized in EDTA-free RIPA buffer containing protease inhibitor (Thermo Scientific) on ice, lysates were separated through 12% SDS-PAGE and blotted onto NC membrane.…”

Section: Reagents and Methodsmentioning

confidence: 99%

Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile

et al. 2016

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Translocator Protein (18kDa, TSPO) is a mitochondrial outer membrane transmembrane protein. Its expression is elevated during inflammation and injury. However, the function of TSPO in vivo is still controversial. Here, we constructed a TSPO global knockout (KO) mouse with a Cre-LoxP system that abolished TSPO protein expression in all tissues and showed normal phenotypes in the physiological condition. The birth rates of TSPO heterozygote (Het) x Het or KO x KO breeding were consistent with Mendel’s Law, suggesting a normal viability of TSPO KO mice at birth. RNA-seq analysis showed no significant difference in the gene expression profile of lung tissues from TSPO KO mice compared with wild type mice, including the genes associated with bronchial alveoli immune homeostasis. The alveolar macrophage population was not affected by TSPO deletion in the physiological condition. Our findings contradict the results of Papadopoulos, but confirmed Selvaraj’s findings. This study confirms TSPO deficiency does not affect viability and bronchial alveolar immune homeostasis.

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Section: Reagents and Methodsmentioning

confidence: 99%

Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile

et al. 2016

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“…6A ). Three important signal pathways, PLC-γ1, MAPK/Erk, and PI3K, are involved in T cell activation 29 . So we applied U73122 (PLC-γ1 inhibitor), UO126 (MAPK/Erk inhibitor), and LY294002 (PI3K inhibitor), and investigated their roles in the upregulation of chemokine receptors on activated Vδ2 T cells, and we found each signaling inhibitor completely abrogated the upregulation of chemokine receptors on Vδ2 T cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Hyperactivation and in situ recruitment of inflammatory Vδ2 T cells contributes to disease pathogenesis in systemic lupus erythematosus

Yin

Mao

et al. 2015

Sci Rep

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In this study, we measured the proportion of peripheral Vδ2 T cells as well as the status and chemokine receptor expression profiles in SLE patients and healthy control (HC). In addition, Vδ2 T cell infiltration in the kidneys of patients with lupus nephritis was examined. The results showed that the percentage of peripheral Vδ2 T cells in new-onset SLE was decreased, and negatively correlated with the SLE Disease Activity Index score and the severity of proteinuria. These cells had a decreased apoptosis but an increased proliferation, and they showed increased accumulation in SLE kidneys. Moreover, IL-21 production and CD40L, CCR4, CCR7, CCR8, CXCR1 and CX3CR1 expression in Vδ2 T cells from SLE patients was significantly higher than from HC (p < 0.05), and these factors were downregulated in association with the repopulation of peripheral Vδ2 T cells in patients who were in remission (p < 0.05). In addition, anti-TCR Vδ2 antibodies activation significantly upregulated these chemokine receptors on Vδ2 T cells from HC, and this effect was blocked by inhibitors of PLC-γ1, MAPK/Erk, and PI3K signaling pathways. Our findings demonstrate that the distribution and function status of Vδ2 T cells from SLE patients are abnormal, and these aberrations may contribute to disease pathogenesis.

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“…Notably, TCR engagement has been shown to be indispensable for γδ T cell-mediated cytotoxicity whereas NKG2D played only a co-stimulatory role; thus indicating the importance of TCR:MIC A complex formation. 73 ULBP molecules may be recognised in a similar manner as it has been shown that ULBP-4 engages both NKG2D and Vγ9Vδ2 TCRs. 74 …”

Section: γδ Tcrs Recognise Tumours In a Co-stimulatory Stress Contextmentioning

confidence: 90%

The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy

2015

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γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of human γδ T cell receptors (TCRs) remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδ T cell compartment in cancer immunosurveillance and paving the way for the use of γδ TCRs in cancer therapy. Ligand recognition by the γδ TCR often requires accessory/co-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδ T cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment.

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Vav1-phospholipase C-γ1 (Vav1-PLC-γ1) Pathway Initiated by T Cell Antigen Receptor (TCRγδ) Activation Is Required to Overcome Inhibition by Ubiquitin Ligase Cbl-b during γδT Cell Cytotoxicity

Cited by 20 publications

References 54 publications

Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile

Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile

Hyperactivation and in situ recruitment of inflammatory Vδ2 T cells contributes to disease pathogenesis in systemic lupus erythematosus

The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy

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