Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip
Antioxidant systems, such as the thioredoxin-1 (Trx1) pathway, ensure cellular redox homeostasis. However, how such systems regulate development and function of myeloid cells is barely understood. Here we show that in contrast to its critical role in T cells, the murine Trx1 system is dispensable fo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/53627 |
| _version_ | 1828221752699781120 |
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| author | Jonathan Muri Helen Thut Qian Feng Manfred Kopf |
| author_facet | Jonathan Muri Helen Thut Qian Feng Manfred Kopf |
| author_sort | Jonathan Muri |
| collection | DOAJ |
| description | Antioxidant systems, such as the thioredoxin-1 (Trx1) pathway, ensure cellular redox homeostasis. However, how such systems regulate development and function of myeloid cells is barely understood. Here we show that in contrast to its critical role in T cells, the murine Trx1 system is dispensable for steady-state myeloid-cell hematopoiesis due to their capacity to tap the glutathione/glutaredoxin pathway for DNA biosynthesis. However, the Trx1 pathway instrumentally enables nuclear NF-κB DNA-binding and thereby pro-inflammatory responses in monocytes and dendritic cells. Moreover, independent of this activity, Trx1 is critical for NLRP3 inflammasome activation and IL-1β production in macrophages by detoxifying excessive ROS levels. Notably, we exclude the involvement of the Trx1 inhibitor Txnip as a redox-sensitive ligand of NLRP3 as previously proposed. Together, this study suggests that targeting Trx1 may be exploited to treat inflammatory diseases. |
| first_indexed | 2024-04-12T16:44:58Z |
| format | Article |
| id | doaj.art-1e23bbe9d08f41edb6f45c6ef69abe67 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:44:58Z |
| publishDate | 2020-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1e23bbe9d08f41edb6f45c6ef69abe672022-12-22T03:24:36ZengeLife Sciences Publications LtdeLife2050-084X2020-02-01910.7554/eLife.53627Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of TxnipJonathan Muri0https://orcid.org/0000-0002-6476-3766Helen Thut1Qian Feng2Manfred Kopf3https://orcid.org/0000-0002-0628-7140Institute of Molecular Health Sciences, ETH Zürich, Zürich, SwitzerlandInstitute of Molecular Health Sciences, ETH Zürich, Zürich, SwitzerlandInstitute of Molecular Health Sciences, ETH Zürich, Zürich, SwitzerlandInstitute of Molecular Health Sciences, ETH Zürich, Zürich, SwitzerlandAntioxidant systems, such as the thioredoxin-1 (Trx1) pathway, ensure cellular redox homeostasis. However, how such systems regulate development and function of myeloid cells is barely understood. Here we show that in contrast to its critical role in T cells, the murine Trx1 system is dispensable for steady-state myeloid-cell hematopoiesis due to their capacity to tap the glutathione/glutaredoxin pathway for DNA biosynthesis. However, the Trx1 pathway instrumentally enables nuclear NF-κB DNA-binding and thereby pro-inflammatory responses in monocytes and dendritic cells. Moreover, independent of this activity, Trx1 is critical for NLRP3 inflammasome activation and IL-1β production in macrophages by detoxifying excessive ROS levels. Notably, we exclude the involvement of the Trx1 inhibitor Txnip as a redox-sensitive ligand of NLRP3 as previously proposed. Together, this study suggests that targeting Trx1 may be exploited to treat inflammatory diseases.https://elifesciences.org/articles/53627nf- kbNLRP3 inflammasomethioredoxin-1glutaredoxinreactive oxygen speciestxnip |
| spellingShingle | Jonathan Muri Helen Thut Qian Feng Manfred Kopf Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip eLife nf- kb NLRP3 inflammasome thioredoxin-1 glutaredoxin reactive oxygen species txnip |
| title | Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip |
| title_full | Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip |
| title_fullStr | Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip |
| title_full_unstemmed | Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip |
| title_short | Thioredoxin-1 distinctly promotes NF-κB target DNA binding and NLRP3 inflammasome activation independently of Txnip |
| title_sort | thioredoxin 1 distinctly promotes nf κb target dna binding and nlrp3 inflammasome activation independently of txnip |
| topic | nf- kb NLRP3 inflammasome thioredoxin-1 glutaredoxin reactive oxygen species txnip |
| url | https://elifesciences.org/articles/53627 |
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