Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE
Abstract Type I Interferon (IFN) was the very first drug approved for the treatment of Multiple Sclerosis (MS), and is still frequently used as a first line therapy. However, systemic IFN also causes considerable side effects, affecting therapy adherence and dose escalation. In addition, the mechani...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-00891-6 |
| _version_ | 1818894422670049280 |
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| author | Anje Cauwels Sandra Van Lint Elke Rogge Annick Verhee Bram Van Den Eeckhout Shengru Pang Marco Prinz Niko Kley Gilles Uzé Jan Tavernier |
| author_facet | Anje Cauwels Sandra Van Lint Elke Rogge Annick Verhee Bram Van Den Eeckhout Shengru Pang Marco Prinz Niko Kley Gilles Uzé Jan Tavernier |
| author_sort | Anje Cauwels |
| collection | DOAJ |
| description | Abstract Type I Interferon (IFN) was the very first drug approved for the treatment of Multiple Sclerosis (MS), and is still frequently used as a first line therapy. However, systemic IFN also causes considerable side effects, affecting therapy adherence and dose escalation. In addition, the mechanism of action of IFN in MS is multifactorial and still not completely understood. Using AcTaferons (Activity-on-Target IFNs, AFNs), optimized IFN-based immunocytokines that allow cell-specific targeting, we have previously demonstrated that specific targeting of IFN activity to dendritic cells (DCs) can protect against experimental autoimmune encephalitis (EAE), inducing in vivo tolerogenic protective effects, evidenced by increased indoleamine-2,3-dioxygenase (IDO) and transforming growth factor β (TGFβ) release by plasmacytoid (p) DCs and improved immunosuppressive capacity of regulatory T and B cells. We here report that targeting type I IFN activity specifically towards B cells also provides strong protection against EAE, and that targeting pDCs using SiglecH-AFN can significantly add to this protective effect. The superior protection achieved by simultaneous targeting of both B lymphocytes and pDCs correlated with improved IL-10 responses in B cells and conventional cDCs, and with a previously unseen very robust IDO response in several cells, including all B and T lymphocytes, cDC1 and cDC2. |
| first_indexed | 2024-12-19T18:28:15Z |
| format | Article |
| id | doaj.art-2d42a731cebf4e52a6429aa1ceb3e0ed |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T18:28:15Z |
| publishDate | 2021-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2d42a731cebf4e52a6429aa1ceb3e0ed2022-12-21T20:10:47ZengNature PortfolioScientific Reports2045-23222021-11-0111111010.1038/s41598-021-00891-6Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAEAnje Cauwels0Sandra Van Lint1Elke Rogge2Annick Verhee3Bram Van Den Eeckhout4Shengru Pang5Marco Prinz6Niko Kley7Gilles Uzé8Jan Tavernier9Cytokine Receptor Laboratory, VIB Medical Biotechnology Center, Ghent UniversityCytokine Receptor Laboratory, VIB Medical Biotechnology Center, Ghent UniversityCytokine Receptor Laboratory, VIB Medical Biotechnology Center, Ghent UniversityCytokine Receptor Laboratory, VIB Medical Biotechnology Center, Ghent UniversityCytokine Receptor Laboratory, VIB Medical Biotechnology Center, Ghent UniversityInstitute of Neuropathology, Faculty of Medicine, University of FreiburgInstitute of Neuropathology, Faculty of Medicine, University of FreiburgOrionis BiosciencesCNRS UMR 5235, University MontpellierCytokine Receptor Laboratory, VIB Medical Biotechnology Center, Ghent UniversityAbstract Type I Interferon (IFN) was the very first drug approved for the treatment of Multiple Sclerosis (MS), and is still frequently used as a first line therapy. However, systemic IFN also causes considerable side effects, affecting therapy adherence and dose escalation. In addition, the mechanism of action of IFN in MS is multifactorial and still not completely understood. Using AcTaferons (Activity-on-Target IFNs, AFNs), optimized IFN-based immunocytokines that allow cell-specific targeting, we have previously demonstrated that specific targeting of IFN activity to dendritic cells (DCs) can protect against experimental autoimmune encephalitis (EAE), inducing in vivo tolerogenic protective effects, evidenced by increased indoleamine-2,3-dioxygenase (IDO) and transforming growth factor β (TGFβ) release by plasmacytoid (p) DCs and improved immunosuppressive capacity of regulatory T and B cells. We here report that targeting type I IFN activity specifically towards B cells also provides strong protection against EAE, and that targeting pDCs using SiglecH-AFN can significantly add to this protective effect. The superior protection achieved by simultaneous targeting of both B lymphocytes and pDCs correlated with improved IL-10 responses in B cells and conventional cDCs, and with a previously unseen very robust IDO response in several cells, including all B and T lymphocytes, cDC1 and cDC2.https://doi.org/10.1038/s41598-021-00891-6 |
| spellingShingle | Anje Cauwels Sandra Van Lint Elke Rogge Annick Verhee Bram Van Den Eeckhout Shengru Pang Marco Prinz Niko Kley Gilles Uzé Jan Tavernier Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE Scientific Reports |
| title | Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE |
| title_full | Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE |
| title_fullStr | Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE |
| title_full_unstemmed | Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE |
| title_short | Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE |
| title_sort | targeting ifn activity to both b cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against eae |
| url | https://doi.org/10.1038/s41598-021-00891-6 |
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