Eintrag weiter verarbeiten
SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells
Gespeichert in:
| Zeitschriftentitel: | The Journal of Immunology |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | The Journal of Immunology, 201, 2018, 6, S. 1671-1680 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The American Association of Immunologists
|
| Schlagwörter: |
| author_facet |
Kim, Yong Chan Kim, Kee Kwang Yoon, Jeongheon Scott, David W. Shevach, Ethan M. Kim, Yong Chan Kim, Kee Kwang Yoon, Jeongheon Scott, David W. Shevach, Ethan M. |
|---|---|
| author |
Kim, Yong Chan Kim, Kee Kwang Yoon, Jeongheon Scott, David W. Shevach, Ethan M. |
| spellingShingle |
Kim, Yong Chan Kim, Kee Kwang Yoon, Jeongheon Scott, David W. Shevach, Ethan M. The Journal of Immunology SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells Immunology Immunology and Allergy |
| author_sort |
kim, yong chan |
| spelling |
Kim, Yong Chan Kim, Kee Kwang Yoon, Jeongheon Scott, David W. Shevach, Ethan M. 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.1800613 <jats:title>Abstract</jats:title> <jats:p>Clinical application of Ag-specific T regulatory cells (Tregs) offers promise for the treatment of undesirable immune diseases. To achieve this goal, long-term expansion of Tregs is required to obtain sufficient numbers of cells. However, human Tregs are not stable ex vivo. Therefore, we previously developed an innovative Treg expansion protocol using 25mer-phosphorothioated random oligonucleotides (ODNps25). The addition of ODNps25 successfully resulted in the stabilization of engineered Ag-specific Tregs; however, the mechanism is not fully characterized. We first identified sterile α motif histidine-aspartate–domain containing protein 1 (SAMHD1) as an ODNps25-binding protein using a UV–cross-linking pull-down strategy. SAMHD1 physically interacted with the 3′ untranslated region of Foxp3 mRNA and was translocated from nucleus to cytoplasm after ODNps25 treatment. Importantly, addition of ODNps25 enhanced the interaction of SAMHD1 and Foxp3 mRNA significantly, and this interaction was increased by TCR stimulation. Because ODNps25 binds to the nuclease (HD) domain of SAMHD1, we then established that overexpression of a dNTPase-deficient mutant (D137N) in Tregs significantly stabilized the expression level of the Foxp3 protein. Furthermore, we found that TCR stimulation upregulates phosphorylation of the threonine residue (Thr592), which is a regulatory site to control SAMHD1 activity, and phosphorylation of Thr592 is critical to control SAMHD1 activity to stabilize the expression of Foxp3 and Helios in Tregs. Taken together, we suggest that the interaction of ODNPs25 in HD or phosphorylation of Thr592 by TCR stimulation interferes with nuclease activity of SAMHD1, thereby stabilizing 3′ untranslated region of Foxp3 and Helios mRNAs in long-term culture.</jats:p> SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells The Journal of Immunology |
| doi_str_mv |
10.4049/jimmunol.1800613 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuNDA0OS9qaW1tdW5vbC4xODAwNjEz |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuNDA0OS9qaW1tdW5vbC4xODAwNjEz |
| institution |
DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 |
| imprint |
The American Association of Immunologists, 2018 |
| imprint_str_mv |
The American Association of Immunologists, 2018 |
| issn |
0022-1767 1550-6606 |
| issn_str_mv |
0022-1767 1550-6606 |
| language |
English |
| mega_collection |
The American Association of Immunologists (CrossRef) |
| match_str |
kim2018samhd1posttranscriptionallycontrolstheexpressionoffoxp3andheliosinhumantregulatorycells |
| publishDateSort |
2018 |
| publisher |
The American Association of Immunologists |
| recordtype |
ai |
| record_format |
ai |
| series |
The Journal of Immunology |
| source_id |
49 |
| title |
SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_unstemmed |
SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_full |
SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_fullStr |
SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_full_unstemmed |
SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_short |
SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_sort |
samhd1 posttranscriptionally controls the expression of foxp3 and helios in human t regulatory cells |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.4049/jimmunol.1800613 |
| publishDate |
2018 |
| physical |
1671-1680 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Clinical application of Ag-specific T regulatory cells (Tregs) offers promise for the treatment of undesirable immune diseases. To achieve this goal, long-term expansion of Tregs is required to obtain sufficient numbers of cells. However, human Tregs are not stable ex vivo. Therefore, we previously developed an innovative Treg expansion protocol using 25mer-phosphorothioated random oligonucleotides (ODNps25). The addition of ODNps25 successfully resulted in the stabilization of engineered Ag-specific Tregs; however, the mechanism is not fully characterized. We first identified sterile α motif histidine-aspartate–domain containing protein 1 (SAMHD1) as an ODNps25-binding protein using a UV–cross-linking pull-down strategy. SAMHD1 physically interacted with the 3′ untranslated region of Foxp3 mRNA and was translocated from nucleus to cytoplasm after ODNps25 treatment. Importantly, addition of ODNps25 enhanced the interaction of SAMHD1 and Foxp3 mRNA significantly, and this interaction was increased by TCR stimulation. Because ODNps25 binds to the nuclease (HD) domain of SAMHD1, we then established that overexpression of a dNTPase-deficient mutant (D137N) in Tregs significantly stabilized the expression level of the Foxp3 protein. Furthermore, we found that TCR stimulation upregulates phosphorylation of the threonine residue (Thr592), which is a regulatory site to control SAMHD1 activity, and phosphorylation of Thr592 is critical to control SAMHD1 activity to stabilize the expression of Foxp3 and Helios in Tregs. Taken together, we suggest that the interaction of ODNPs25 in HD or phosphorylation of Thr592 by TCR stimulation interferes with nuclease activity of SAMHD1, thereby stabilizing 3′ untranslated region of Foxp3 and Helios mRNAs in long-term culture.</jats:p> |
| container_issue |
6 |
| container_start_page |
1671 |
| container_title |
The Journal of Immunology |
| container_volume |
201 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792340856118706183 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T16:10:39.088Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=SAMHD1+Posttranscriptionally+Controls+the+Expression+of+Foxp3+and+Helios+in+Human+T+Regulatory+Cells&rft.date=2018-09-15&genre=article&issn=1550-6606&volume=201&issue=6&spage=1671&epage=1680&pages=1671-1680&jtitle=The+Journal+of+Immunology&atitle=SAMHD1+Posttranscriptionally+Controls+the+Expression+of+Foxp3+and+Helios+in+Human+T+Regulatory+Cells&aulast=Shevach&aufirst=Ethan+M.&rft_id=info%3Adoi%2F10.4049%2Fjimmunol.1800613&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792340856118706183 |
| author | Kim, Yong Chan, Kim, Kee Kwang, Yoon, Jeongheon, Scott, David W., Shevach, Ethan M. |
| author_facet | Kim, Yong Chan, Kim, Kee Kwang, Yoon, Jeongheon, Scott, David W., Shevach, Ethan M., Kim, Yong Chan, Kim, Kee Kwang, Yoon, Jeongheon, Scott, David W., Shevach, Ethan M. |
| author_sort | kim, yong chan |
| container_issue | 6 |
| container_start_page | 1671 |
| container_title | The Journal of Immunology |
| container_volume | 201 |
| description | <jats:title>Abstract</jats:title> <jats:p>Clinical application of Ag-specific T regulatory cells (Tregs) offers promise for the treatment of undesirable immune diseases. To achieve this goal, long-term expansion of Tregs is required to obtain sufficient numbers of cells. However, human Tregs are not stable ex vivo. Therefore, we previously developed an innovative Treg expansion protocol using 25mer-phosphorothioated random oligonucleotides (ODNps25). The addition of ODNps25 successfully resulted in the stabilization of engineered Ag-specific Tregs; however, the mechanism is not fully characterized. We first identified sterile α motif histidine-aspartate–domain containing protein 1 (SAMHD1) as an ODNps25-binding protein using a UV–cross-linking pull-down strategy. SAMHD1 physically interacted with the 3′ untranslated region of Foxp3 mRNA and was translocated from nucleus to cytoplasm after ODNps25 treatment. Importantly, addition of ODNps25 enhanced the interaction of SAMHD1 and Foxp3 mRNA significantly, and this interaction was increased by TCR stimulation. Because ODNps25 binds to the nuclease (HD) domain of SAMHD1, we then established that overexpression of a dNTPase-deficient mutant (D137N) in Tregs significantly stabilized the expression level of the Foxp3 protein. Furthermore, we found that TCR stimulation upregulates phosphorylation of the threonine residue (Thr592), which is a regulatory site to control SAMHD1 activity, and phosphorylation of Thr592 is critical to control SAMHD1 activity to stabilize the expression of Foxp3 and Helios in Tregs. Taken together, we suggest that the interaction of ODNPs25 in HD or phosphorylation of Thr592 by TCR stimulation interferes with nuclease activity of SAMHD1, thereby stabilizing 3′ untranslated region of Foxp3 and Helios mRNAs in long-term culture.</jats:p> |
| doi_str_mv | 10.4049/jimmunol.1800613 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuNDA0OS9qaW1tdW5vbC4xODAwNjEz |
| imprint | The American Association of Immunologists, 2018 |
| imprint_str_mv | The American Association of Immunologists, 2018 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14 |
| issn | 0022-1767, 1550-6606 |
| issn_str_mv | 0022-1767, 1550-6606 |
| language | English |
| last_indexed | 2024-03-01T16:10:39.088Z |
| match_str | kim2018samhd1posttranscriptionallycontrolstheexpressionoffoxp3andheliosinhumantregulatorycells |
| mega_collection | The American Association of Immunologists (CrossRef) |
| physical | 1671-1680 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| publisher | The American Association of Immunologists |
| record_format | ai |
| recordtype | ai |
| series | The Journal of Immunology |
| source_id | 49 |
| spelling | Kim, Yong Chan Kim, Kee Kwang Yoon, Jeongheon Scott, David W. Shevach, Ethan M. 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.1800613 <jats:title>Abstract</jats:title> <jats:p>Clinical application of Ag-specific T regulatory cells (Tregs) offers promise for the treatment of undesirable immune diseases. To achieve this goal, long-term expansion of Tregs is required to obtain sufficient numbers of cells. However, human Tregs are not stable ex vivo. Therefore, we previously developed an innovative Treg expansion protocol using 25mer-phosphorothioated random oligonucleotides (ODNps25). The addition of ODNps25 successfully resulted in the stabilization of engineered Ag-specific Tregs; however, the mechanism is not fully characterized. We first identified sterile α motif histidine-aspartate–domain containing protein 1 (SAMHD1) as an ODNps25-binding protein using a UV–cross-linking pull-down strategy. SAMHD1 physically interacted with the 3′ untranslated region of Foxp3 mRNA and was translocated from nucleus to cytoplasm after ODNps25 treatment. Importantly, addition of ODNps25 enhanced the interaction of SAMHD1 and Foxp3 mRNA significantly, and this interaction was increased by TCR stimulation. Because ODNps25 binds to the nuclease (HD) domain of SAMHD1, we then established that overexpression of a dNTPase-deficient mutant (D137N) in Tregs significantly stabilized the expression level of the Foxp3 protein. Furthermore, we found that TCR stimulation upregulates phosphorylation of the threonine residue (Thr592), which is a regulatory site to control SAMHD1 activity, and phosphorylation of Thr592 is critical to control SAMHD1 activity to stabilize the expression of Foxp3 and Helios in Tregs. Taken together, we suggest that the interaction of ODNPs25 in HD or phosphorylation of Thr592 by TCR stimulation interferes with nuclease activity of SAMHD1, thereby stabilizing 3′ untranslated region of Foxp3 and Helios mRNAs in long-term culture.</jats:p> SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells The Journal of Immunology |
| spellingShingle | Kim, Yong Chan, Kim, Kee Kwang, Yoon, Jeongheon, Scott, David W., Shevach, Ethan M., The Journal of Immunology, SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells, Immunology, Immunology and Allergy |
| title | SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_full | SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_fullStr | SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_full_unstemmed | SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_short | SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| title_sort | samhd1 posttranscriptionally controls the expression of foxp3 and helios in human t regulatory cells |
| title_unstemmed | SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human T Regulatory Cells |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.4049/jimmunol.1800613 |