Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.

Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are central to the initiation and the regulation of immune processes in multiple sclerosis (MS). Natalizumab (NTZ) is a humanized monoclonal antibody approved for the treatment of MS that acts by blocking expression of VLA-4 integrins on the surf...

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Autores principales:	Clara de Andrés, Roseta Teijeiro, Bárbara Alonso, Francisco Sánchez-Madrid, M Luisa Martínez, Juan Guzmán de Villoria, Eduardo Fernández-Cruz, Silvia Sánchez-Ramón
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e8409bcf16b04217b4b183af45ff3b6c
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spelling	oai:doaj.org-article:e8409bcf16b04217b4b183af45ff3b6c2021-11-18T07:23:16ZLong-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.1932-620310.1371/journal.pone.0034103https://doaj.org/article/e8409bcf16b04217b4b183af45ff3b6c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496780/?tool=EBIhttps://doaj.org/toc/1932-6203Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are central to the initiation and the regulation of immune processes in multiple sclerosis (MS). Natalizumab (NTZ) is a humanized monoclonal antibody approved for the treatment of MS that acts by blocking expression of VLA-4 integrins on the surface of leukocytes. We determined the proportions of circulating DC subsets and analyzed expression of VLA-4 expression in 6 relapsing-remitting MS patients treated with NTZ for 1 year. VLA-4 expression levels on pDCs and mDCs decreased significantly during follow-up. In vitro coculture of peripheral blood mononuclear cells and pDCs, with different doses of NTZ in healthy controls (HC) and MS patients showed dose-dependent down-regulation of VLA-4 expression levels in both MS patients and HC, and reduced functional ability to stimulate antigen-specific T-lymphocyte responses. The biological impact of NTZ may in part be attributable to inhibition of transmigration of circulating DCs into the central nervous system, but also to functional impairment of interactions between T cells and DC.Clara de AndrésRoseta TeijeiroBárbara AlonsoFrancisco Sánchez-MadridM Luisa MartínezJuan Guzmán de VilloriaEduardo Fernández-CruzSilvia Sánchez-RamónPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34103 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Clara de Andrés Roseta Teijeiro Bárbara Alonso Francisco Sánchez-Madrid M Luisa Martínez Juan Guzmán de Villoria Eduardo Fernández-Cruz Silvia Sánchez-Ramón Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.
description	Myeloid and plasmacytoid dendritic cells (mDCs, pDCs) are central to the initiation and the regulation of immune processes in multiple sclerosis (MS). Natalizumab (NTZ) is a humanized monoclonal antibody approved for the treatment of MS that acts by blocking expression of VLA-4 integrins on the surface of leukocytes. We determined the proportions of circulating DC subsets and analyzed expression of VLA-4 expression in 6 relapsing-remitting MS patients treated with NTZ for 1 year. VLA-4 expression levels on pDCs and mDCs decreased significantly during follow-up. In vitro coculture of peripheral blood mononuclear cells and pDCs, with different doses of NTZ in healthy controls (HC) and MS patients showed dose-dependent down-regulation of VLA-4 expression levels in both MS patients and HC, and reduced functional ability to stimulate antigen-specific T-lymphocyte responses. The biological impact of NTZ may in part be attributable to inhibition of transmigration of circulating DCs into the central nervous system, but also to functional impairment of interactions between T cells and DC.
format	article
author	Clara de Andrés Roseta Teijeiro Bárbara Alonso Francisco Sánchez-Madrid M Luisa Martínez Juan Guzmán de Villoria Eduardo Fernández-Cruz Silvia Sánchez-Ramón
author_facet	Clara de Andrés Roseta Teijeiro Bárbara Alonso Francisco Sánchez-Madrid M Luisa Martínez Juan Guzmán de Villoria Eduardo Fernández-Cruz Silvia Sánchez-Ramón
author_sort	Clara de Andrés
title	Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.
title_short	Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.
title_full	Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.
title_fullStr	Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.
title_full_unstemmed	Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.
title_sort	long-term decrease in vla-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e8409bcf16b04217b4b183af45ff3b6c
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Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis.

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