221
Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the correspondi...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Salerno, Fiamma [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2013transfer abstract |
|---|
| Übergeordnetes Werk: |
Enthalten in: The minimal clinically important differences of the Simple Shoulder Test are different for different arthroplasty types - McLaughlin, Richard J. ELSEVIER, 2022, the official journal of the International Cytokine Society, Oxford [u.a.] |
|---|---|
| Übergeordnetes Werk: |
volume:63 ; year:2013 ; number:3 ; pages:295 |
| Links: |
|---|
| DOI / URN: |
10.1016/j.cyto.2013.06.224 |
|---|
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ELV022163352 |
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| 520 | |a Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. | ||
| 520 | |a Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. | ||
| 700 | 1 | |a Engels, Sander |4 oth | |
| 700 | 1 | |a Zhao, Wanqi |4 oth | |
| 700 | 1 | |a Hodge, Deborah |4 oth | |
| 700 | 1 | |a Young, Howard A. |4 oth | |
| 700 | 1 | |a Medema, Jan Paul |4 oth | |
| 700 | 1 | |a Wolkers, Monika C. |4 oth | |
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10.1016/j.cyto.2013.06.224 doi GBVA2013017000028.pica (DE-627)ELV022163352 (ELSEVIER)S1043-4666(13)00498-5 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 44.83 bkl Salerno, Fiamma verfasserin aut 221 2013transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Engels, Sander oth Zhao, Wanqi oth Hodge, Deborah oth Young, Howard A. oth Medema, Jan Paul oth Wolkers, Monika C. oth Enthalten in Elsevier McLaughlin, Richard J. ELSEVIER The minimal clinically important differences of the Simple Shoulder Test are different for different arthroplasty types 2022 the official journal of the International Cytokine Society Oxford [u.a.] (DE-627)ELV008219540 volume:63 year:2013 number:3 pages:295 https://doi.org/10.1016/j.cyto.2013.06.224 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.83 Rheumatologie Orthopädie VZ AR 63 2013 3 295 045F 570 |
| spelling |
10.1016/j.cyto.2013.06.224 doi GBVA2013017000028.pica (DE-627)ELV022163352 (ELSEVIER)S1043-4666(13)00498-5 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 44.83 bkl Salerno, Fiamma verfasserin aut 221 2013transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Engels, Sander oth Zhao, Wanqi oth Hodge, Deborah oth Young, Howard A. oth Medema, Jan Paul oth Wolkers, Monika C. oth Enthalten in Elsevier McLaughlin, Richard J. ELSEVIER The minimal clinically important differences of the Simple Shoulder Test are different for different arthroplasty types 2022 the official journal of the International Cytokine Society Oxford [u.a.] (DE-627)ELV008219540 volume:63 year:2013 number:3 pages:295 https://doi.org/10.1016/j.cyto.2013.06.224 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.83 Rheumatologie Orthopädie VZ AR 63 2013 3 295 045F 570 |
| allfields_unstemmed |
10.1016/j.cyto.2013.06.224 doi GBVA2013017000028.pica (DE-627)ELV022163352 (ELSEVIER)S1043-4666(13)00498-5 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 44.83 bkl Salerno, Fiamma verfasserin aut 221 2013transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Engels, Sander oth Zhao, Wanqi oth Hodge, Deborah oth Young, Howard A. oth Medema, Jan Paul oth Wolkers, Monika C. oth Enthalten in Elsevier McLaughlin, Richard J. ELSEVIER The minimal clinically important differences of the Simple Shoulder Test are different for different arthroplasty types 2022 the official journal of the International Cytokine Society Oxford [u.a.] (DE-627)ELV008219540 volume:63 year:2013 number:3 pages:295 https://doi.org/10.1016/j.cyto.2013.06.224 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.83 Rheumatologie Orthopädie VZ AR 63 2013 3 295 045F 570 |
| allfieldsGer |
10.1016/j.cyto.2013.06.224 doi GBVA2013017000028.pica (DE-627)ELV022163352 (ELSEVIER)S1043-4666(13)00498-5 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 44.83 bkl Salerno, Fiamma verfasserin aut 221 2013transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Engels, Sander oth Zhao, Wanqi oth Hodge, Deborah oth Young, Howard A. oth Medema, Jan Paul oth Wolkers, Monika C. oth Enthalten in Elsevier McLaughlin, Richard J. ELSEVIER The minimal clinically important differences of the Simple Shoulder Test are different for different arthroplasty types 2022 the official journal of the International Cytokine Society Oxford [u.a.] (DE-627)ELV008219540 volume:63 year:2013 number:3 pages:295 https://doi.org/10.1016/j.cyto.2013.06.224 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.83 Rheumatologie Orthopädie VZ AR 63 2013 3 295 045F 570 |
| allfieldsSound |
10.1016/j.cyto.2013.06.224 doi GBVA2013017000028.pica (DE-627)ELV022163352 (ELSEVIER)S1043-4666(13)00498-5 DE-627 ger DE-627 rakwb eng 570 570 DE-600 610 VZ 44.83 bkl Salerno, Fiamma verfasserin aut 221 2013transfer abstract nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. Engels, Sander oth Zhao, Wanqi oth Hodge, Deborah oth Young, Howard A. oth Medema, Jan Paul oth Wolkers, Monika C. oth Enthalten in Elsevier McLaughlin, Richard J. ELSEVIER The minimal clinically important differences of the Simple Shoulder Test are different for different arthroplasty types 2022 the official journal of the International Cytokine Society Oxford [u.a.] (DE-627)ELV008219540 volume:63 year:2013 number:3 pages:295 https://doi.org/10.1016/j.cyto.2013.06.224 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA 44.83 Rheumatologie Orthopädie VZ AR 63 2013 3 295 045F 570 |
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Enthalten in The minimal clinically important differences of the Simple Shoulder Test are different for different arthroplasty types Oxford [u.a.] volume:63 year:2013 number:3 pages:295 |
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The minimal clinically important differences of the Simple Shoulder Test are different for different arthroplasty types |
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Salerno, Fiamma @@aut@@ Engels, Sander @@oth@@ Zhao, Wanqi @@oth@@ Hodge, Deborah @@oth@@ Young, Howard A. @@oth@@ Medema, Jan Paul @@oth@@ Wolkers, Monika C. @@oth@@ |
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Memory CD8+ T cells are pivotal to protect us from recurring infections. They prevent pathogen spreading at early stages of reinfection through rapid release of effector molecules. Strikingly, while resting memory T cells express high levels of cytokine transcripts, the production of the corresponding proteins is blocked unless T cells are reactivated. This indicates that translation of cytokine mRNA is strictly regulated in memory T cells. Here, we investigate how the production of interferon gamma (IFN-γ) is controlled in memory T cells. IFN-γ is a pro-inflammatory cytokine that is required to control microbial infections, however, aberrant expression is associated with immunopathology. By using reporter gene analysis we demonstrate that IFN-γ production is tightly regulated via a 3′untranslated region (3′UTR)-dependent mechanism in CD8+ T cells both in vitro and in vivo. We observed that the highly conserved AU-rich elements (AREs) within the first 253 nucleotides of the IFN-γ 3′UTR govern this mechanism. Importantly, we show that the regulation of IFN-γ through AREs is maintained in CD4+ and CD8+ T cells and is highly conserved in human and mouse. Moreover, germ-line deletion of the ARE-containing region within the IFN-γ 3′UTR abrogates both post-transcriptional and translational regulation, as determined by an increased stability of IFN-γ mRNA and hyper-responsiveness of memory T cells. Taken together, these findings indicate that AU-rich elements within the IFN-γ 3′UTR comprise a crucial component that keeps memory T cell responses in check and is essential for a protective, yet balanced immune response. Unraveling the molecular mechanisms that govern this tight control of cytokine production will help design strategies to manipulate impaired T cell responses. |
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