Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell program
Regulatory T cells (Tregs) play a central role in modulating adaptive immune responses in humans and mice. The precise biological role of non-canonical nuclear factor ‘κ-light-chain-enhancer’ of activated B cells (NFKB) signaling in human Tregs has yet to be fully elucidated. To gain insight into th...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023101198 |
| _version_ | 1797383937200226304 |
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| author | Yohei Sato Erika Osada Yoshinobu Manome |
| author_facet | Yohei Sato Erika Osada Yoshinobu Manome |
| author_sort | Yohei Sato |
| collection | DOAJ |
| description | Regulatory T cells (Tregs) play a central role in modulating adaptive immune responses in humans and mice. The precise biological role of non-canonical nuclear factor ‘κ-light-chain-enhancer’ of activated B cells (NFKB) signaling in human Tregs has yet to be fully elucidated. To gain insight into this process, a Treg-like cell line (MT-2) was genetically modified using CRISPR/Cas9. Interestingly, NFKB2 knockout MT-2 cells exhibited downregulation of FOXP3, while NFKB1 knockout did not. Additionally, mRNA expression of FOXP3-dependent molecules was significantly reduced in NFKB2 knockout MT-2 cells. To better understand the functional role of the NFKB signaling, the NFKB1/NFKB2 loci of human primary Tregs were genetically edited using CRISPR/Cas9. Similar to MT-2 cells, NFKB2 knockout human Tregs displayed significantly reduced FOXP3 expression. Furthermore, NFKB2 knockout human Tregs showed downregulation of FOXP3-dependent molecules and a diminished suppressive function compared to wild-type and NFKB1 knockout Tregs. These findings indicate that non-canonical NFKB signaling maintains a Treg-like phenotype and suppressive function in human Tregs through the FOXP3-dependent regulatory T cell program. |
| first_indexed | 2024-03-08T21:28:13Z |
| format | Article |
| id | doaj.art-6e2671d589c24504a3b88d615b8c09d2 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T21:28:13Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-6e2671d589c24504a3b88d615b8c09d22023-12-21T07:35:07ZengElsevierHeliyon2405-84402023-12-01912e22911Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell programYohei Sato0Erika Osada1Yoshinobu Manome2Corresponding author. 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, Japan.; Core Research Facilities, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, JapanCore Research Facilities, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, JapanCore Research Facilities, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, JapanRegulatory T cells (Tregs) play a central role in modulating adaptive immune responses in humans and mice. The precise biological role of non-canonical nuclear factor ‘κ-light-chain-enhancer’ of activated B cells (NFKB) signaling in human Tregs has yet to be fully elucidated. To gain insight into this process, a Treg-like cell line (MT-2) was genetically modified using CRISPR/Cas9. Interestingly, NFKB2 knockout MT-2 cells exhibited downregulation of FOXP3, while NFKB1 knockout did not. Additionally, mRNA expression of FOXP3-dependent molecules was significantly reduced in NFKB2 knockout MT-2 cells. To better understand the functional role of the NFKB signaling, the NFKB1/NFKB2 loci of human primary Tregs were genetically edited using CRISPR/Cas9. Similar to MT-2 cells, NFKB2 knockout human Tregs displayed significantly reduced FOXP3 expression. Furthermore, NFKB2 knockout human Tregs showed downregulation of FOXP3-dependent molecules and a diminished suppressive function compared to wild-type and NFKB1 knockout Tregs. These findings indicate that non-canonical NFKB signaling maintains a Treg-like phenotype and suppressive function in human Tregs through the FOXP3-dependent regulatory T cell program.http://www.sciencedirect.com/science/article/pii/S2405844023101198Regulatory T cellsNFKB signalingCRISPR/Cas9FOXP3Suppressive function |
| spellingShingle | Yohei Sato Erika Osada Yoshinobu Manome Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell program Heliyon Regulatory T cells NFKB signaling CRISPR/Cas9 FOXP3 Suppressive function |
| title | Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell program |
| title_full | Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell program |
| title_fullStr | Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell program |
| title_full_unstemmed | Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell program |
| title_short | Non-canonical NFKB signaling endows suppressive function through FOXP3-dependent regulatory T cell program |
| title_sort | non canonical nfkb signaling endows suppressive function through foxp3 dependent regulatory t cell program |
| topic | Regulatory T cells NFKB signaling CRISPR/Cas9 FOXP3 Suppressive function |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023101198 |
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