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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Autores principales:	Anje Cauwels, Sandra Van Lint, Elke Rogge, Annick Verhee, Bram Van Den Eeckhout, Shengru Pang, Marco Prinz, Niko Kley, Gilles Uzé, Jan Tavernier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2d42a731cebf4e52a6429aa1ceb3e0ed
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spelling	oai:doaj.org-article:2d42a731cebf4e52a6429aa1ceb3e0ed2021-11-08T10:52:37ZTargeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE10.1038/s41598-021-00891-62045-2322https://doaj.org/article/2d42a731cebf4e52a6429aa1ceb3e0ed2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00891-6https://doaj.org/toc/2045-2322Abstract 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.Anje CauwelsSandra Van LintElke RoggeAnnick VerheeBram Van Den EeckhoutShengru PangMarco PrinzNiko KleyGilles UzéJan TavernierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	targeting ifn activity to both b cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against eae
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2d42a731cebf4e52a6429aa1ceb3e0ed
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Targeting IFN activity to both B cells and plasmacytoid dendritic cells induces a robust tolerogenic response and protection against EAE

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