pERK-dependent defective TCR-mediated activation of CD4+ T cells in end-stage renal disease patients
Abstract Background Patients with end-stage renal disease (ESRD) have an impaired immune response with a prematurely aged T-cell system. Mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) and p38, regulate diverse cellular programs by transferring extrace...
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BioMed Central
2017-06-01
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| Series: | Immunity & Ageing |
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| Online Access: | http://link.springer.com/article/10.1186/s12979-017-0096-1 |
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doaj-art-7060b6c5185b4bfe94a978062f620a572018-08-21T10:47:26ZengBioMed CentralImmunity & Ageing1742-49332017-06-0114111410.1186/s12979-017-0096-1pERK-dependent defective TCR-mediated activation of CD4+ T cells in end-stage renal disease patientsLing Huang0Nicolle H. R. Litjens1Nynke M. Kannegieter2Mariska Klepper3Carla C. Baan4Michiel G. H. Betjes5Department of Internal Medicine, Section Nephrology and Transplantation, Erasmus University Medical CenterDepartment of Internal Medicine, Section Nephrology and Transplantation, Erasmus University Medical CenterDepartment of Internal Medicine, Section Nephrology and Transplantation, Erasmus University Medical CenterDepartment of Internal Medicine, Section Nephrology and Transplantation, Erasmus University Medical CenterDepartment of Internal Medicine, Section Nephrology and Transplantation, Erasmus University Medical CenterDepartment of Internal Medicine, Section Nephrology and Transplantation, Erasmus University Medical CenterAbstract Background Patients with end-stage renal disease (ESRD) have an impaired immune response with a prematurely aged T-cell system. Mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) and p38, regulate diverse cellular programs by transferring extracellular signals into an intracellular response. T cell receptor (TCR)-induced phosphorylation of ERK (pERK) may show an age-associated decline, which can be reversed by inhibiting dual specific phosphatase (DUSP) 6, a cytoplasmic phosphatase with substrate specificity to dephosphorylate pERK. The aim of this study was to assess whether ESRD affects TCR-mediated signaling and explore possibilities for intervening in ESRD-associated defective T-cell mediated immunity. Results An age-associated decline in TCR-induced pERK-levels was observed in the different CD4+ (P < 0.05), but not CD8+, T-cell subsets from healthy individuals (HI). Interestingly, pERK-levels of CD4+ T-cell subsets from young ESRD patients were in between young and elderly HI. A differentiation-associated decline in TCR-induced ERK and p38 phosphorylation was observed in T cells, although TCR-induced p38 phosphorylation was not significantly affected by age and/or ESRD. Frequencies of TCR-induced CD69-expressing CD4+ T cells declined with age and were positively associated with pERK. In addition, an age-associated tendency of increased expression of DUSP6 was observed in CD4+ T cells of HI and DUSP6 expression in young ESRD patients was similar to old HI. Inhibition of DUSP6 significantly increased TCR-induced pERK-levels of CD4+ T cells in young and elderly ESRD patients, and elderly HI. Conclusions TCR-mediated phosphorylation of ERK is affected in young ESRD patients consistent with the concept of premature immunological T cell ageing. Inhibition of DUSP6 specific for pERK might be a potential intervention enhancing T-cell mediated immunity in ESRD patients.http://link.springer.com/article/10.1186/s12979-017-0096-1ESRDT cellsERKp38DUSP 6MAPK |
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| language |
English |
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Article |
| author |
Ling Huang Nicolle H. R. Litjens Nynke M. Kannegieter Mariska Klepper Carla C. Baan Michiel G. H. Betjes |
| spellingShingle |
Ling Huang Nicolle H. R. Litjens Nynke M. Kannegieter Mariska Klepper Carla C. Baan Michiel G. H. Betjes pERK-dependent defective TCR-mediated activation of CD4+ T cells in end-stage renal disease patients Immunity & Ageing ESRD T cells ERK p38 DUSP 6 MAPK |
| author_facet |
Ling Huang Nicolle H. R. Litjens Nynke M. Kannegieter Mariska Klepper Carla C. Baan Michiel G. H. Betjes |
| author_sort |
Ling Huang |
| title |
pERK-dependent defective TCR-mediated activation of CD4+ T cells in end-stage renal disease patients |
| title_short |
pERK-dependent defective TCR-mediated activation of CD4+ T cells in end-stage renal disease patients |
| title_full |
pERK-dependent defective TCR-mediated activation of CD4+ T cells in end-stage renal disease patients |
| title_fullStr |
pERK-dependent defective TCR-mediated activation of CD4+ T cells in end-stage renal disease patients |
| title_full_unstemmed |
pERK-dependent defective TCR-mediated activation of CD4+ T cells in end-stage renal disease patients |
| title_sort |
perk-dependent defective tcr-mediated activation of cd4+ t cells in end-stage renal disease patients |
| publisher |
BioMed Central |
| series |
Immunity & Ageing |
| issn |
1742-4933 |
| publishDate |
2017-06-01 |
| description |
Abstract Background Patients with end-stage renal disease (ESRD) have an impaired immune response with a prematurely aged T-cell system. Mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK) and p38, regulate diverse cellular programs by transferring extracellular signals into an intracellular response. T cell receptor (TCR)-induced phosphorylation of ERK (pERK) may show an age-associated decline, which can be reversed by inhibiting dual specific phosphatase (DUSP) 6, a cytoplasmic phosphatase with substrate specificity to dephosphorylate pERK. The aim of this study was to assess whether ESRD affects TCR-mediated signaling and explore possibilities for intervening in ESRD-associated defective T-cell mediated immunity. Results An age-associated decline in TCR-induced pERK-levels was observed in the different CD4+ (P < 0.05), but not CD8+, T-cell subsets from healthy individuals (HI). Interestingly, pERK-levels of CD4+ T-cell subsets from young ESRD patients were in between young and elderly HI. A differentiation-associated decline in TCR-induced ERK and p38 phosphorylation was observed in T cells, although TCR-induced p38 phosphorylation was not significantly affected by age and/or ESRD. Frequencies of TCR-induced CD69-expressing CD4+ T cells declined with age and were positively associated with pERK. In addition, an age-associated tendency of increased expression of DUSP6 was observed in CD4+ T cells of HI and DUSP6 expression in young ESRD patients was similar to old HI. Inhibition of DUSP6 significantly increased TCR-induced pERK-levels of CD4+ T cells in young and elderly ESRD patients, and elderly HI. Conclusions TCR-mediated phosphorylation of ERK is affected in young ESRD patients consistent with the concept of premature immunological T cell ageing. Inhibition of DUSP6 specific for pERK might be a potential intervention enhancing T-cell mediated immunity in ESRD patients. |
| topic |
ESRD T cells ERK p38 DUSP 6 MAPK |
| url |
http://link.springer.com/article/10.1186/s12979-017-0096-1 |
| _version_ |
1612682118528237568 |