Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis

Abstract Early innate education of hematopoietic progenitors within the bone marrow (BM) stably primes them for either trained immunity or instead immunoregulatory functions. We herein demonstrate that in vivo or in vitro activation within the BM via Toll-like receptor-9 generates a population of pl...

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Autores principales:	Hélène Letscher, Viviane A. Agbogan, Sarantis Korniotis, Pauline Gastineau, Emmanuel Tejerina, Christophe Gras, Jérôme Mégret, Alison Moe, William R. Drobyski, Flora Zavala
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4fd5c13ee9141009cc44b6049bbacf9
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spelling	oai:doaj.org-article:c4fd5c13ee9141009cc44b6049bbacf92021-12-02T13:19:22ZToll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis10.1038/s41598-021-84023-02045-2322https://doaj.org/article/c4fd5c13ee9141009cc44b6049bbacf92021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84023-0https://doaj.org/toc/2045-2322Abstract Early innate education of hematopoietic progenitors within the bone marrow (BM) stably primes them for either trained immunity or instead immunoregulatory functions. We herein demonstrate that in vivo or in vitro activation within the BM via Toll-like receptor-9 generates a population of plasmacytoid dendritic cell (pDC) precursors (CpG-pre-pDCs) that, unlike pDC precursors isolated from PBS-incubated BM (PBS-pre-pDCs), are endowed with the capacity to halt progression of ongoing experimental autoimmune encephalomyelitis. CpG activation enhances the selective migration of pDC precursors to the inflamed spinal cord, induces their immediate production of TGF-β, and after migration, of enhanced levels of IL-27. CpG-pre-pDC derived TGF-β and IL-27 ensure protection at early and late phases of the disease, respectively. Spinal cords of CpG-pre-pDC-protected recipient mice display enhanced percentages of host-derived pDCs expressing TGF-β as well as an accumulation of IL-10 producing B cells and of CD11c+ CD11b+ dendritic cells. These results reveal that pDC precursors are conferred stable therapeutic properties by early innate activation within the BM. They further extend to the pDC lineage promising perspectives for cell therapy of autoimmune diseases with innate activated hematopoietic precursor cells.Hélène LetscherViviane A. AgboganSarantis KorniotisPauline GastineauEmmanuel TejerinaChristophe GrasJérôme MégretAlison MoeWilliam R. DrobyskiFlora ZavalaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hélène Letscher Viviane A. Agbogan Sarantis Korniotis Pauline Gastineau Emmanuel Tejerina Christophe Gras Jérôme Mégret Alison Moe William R. Drobyski Flora Zavala Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis
description	Abstract Early innate education of hematopoietic progenitors within the bone marrow (BM) stably primes them for either trained immunity or instead immunoregulatory functions. We herein demonstrate that in vivo or in vitro activation within the BM via Toll-like receptor-9 generates a population of plasmacytoid dendritic cell (pDC) precursors (CpG-pre-pDCs) that, unlike pDC precursors isolated from PBS-incubated BM (PBS-pre-pDCs), are endowed with the capacity to halt progression of ongoing experimental autoimmune encephalomyelitis. CpG activation enhances the selective migration of pDC precursors to the inflamed spinal cord, induces their immediate production of TGF-β, and after migration, of enhanced levels of IL-27. CpG-pre-pDC derived TGF-β and IL-27 ensure protection at early and late phases of the disease, respectively. Spinal cords of CpG-pre-pDC-protected recipient mice display enhanced percentages of host-derived pDCs expressing TGF-β as well as an accumulation of IL-10 producing B cells and of CD11c+ CD11b+ dendritic cells. These results reveal that pDC precursors are conferred stable therapeutic properties by early innate activation within the BM. They further extend to the pDC lineage promising perspectives for cell therapy of autoimmune diseases with innate activated hematopoietic precursor cells.
format	article
author	Hélène Letscher Viviane A. Agbogan Sarantis Korniotis Pauline Gastineau Emmanuel Tejerina Christophe Gras Jérôme Mégret Alison Moe William R. Drobyski Flora Zavala
author_facet	Hélène Letscher Viviane A. Agbogan Sarantis Korniotis Pauline Gastineau Emmanuel Tejerina Christophe Gras Jérôme Mégret Alison Moe William R. Drobyski Flora Zavala
author_sort	Hélène Letscher
title	Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis
title_short	Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis
title_full	Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis
title_fullStr	Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis
title_full_unstemmed	Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis
title_sort	toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c4fd5c13ee9141009cc44b6049bbacf9
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Toll-like receptor-9 stimulated plasmacytoid dendritic cell precursors suppress autoimmune neuroinflammation in a murine model of multiple sclerosis

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