Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity

Abstract The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Her...

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Autores principales:	Divya Sagar, Narendra P. Singh, Rashida Ginwala, Xiaofang Huang, Ramila Philip, Mitzi Nagarkatti, Prakash Nagarkatti, Konstantin Neumann, Jürgen Ruland, Allison M. Andrews, Servio H. Ramirez, Zafar K. Khan, Pooja Jain
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Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3480ad339694c2197a255d3370edaa6
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spelling	oai:doaj.org-article:f3480ad339694c2197a255d3370edaa62021-12-02T11:52:22ZAntibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity10.1038/s41598-017-03027-x2045-2322https://doaj.org/article/f3480ad339694c2197a255d3370edaa62017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03027-xhttps://doaj.org/toc/2045-2322Abstract The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Here, we identified functions of one C-type lectin receptor, CLEC12A, in facilitating DC binding and transmigration across the BBB in response to CCL2 chemotaxis. To test function of CLEC12A in an animal model of multiple sclerosis (MS), we administered blocking antibody to CLEC12A that significantly ameliorated disease scores in MOG35–55-induced progressive, as well as PLP138–151-induced relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice. The decline in both progression and relapse of EAE occurred as a result of reduced demyelination and myeloid cell infiltration into the CNS tissue. DC numbers were restored in the spleen of C57BL/6 and peripheral blood of SJL/J mice along with a decreased TH17 phenotype within CD4+ T-cells. The effects of CLEC12A blocking were further validated using CLEC12A knockout (KO) animals wherein EAE disease induction was delayed and reduced disease severity was observed. These studies reveal the utility of a DC-specific mechanism in designing new therapeutics for MS.Divya SagarNarendra P. SinghRashida GinwalaXiaofang HuangRamila PhilipMitzi NagarkattiPrakash NagarkattiKonstantin NeumannJürgen RulandAllison M. AndrewsServio H. RamirezZafar K. KhanPooja JainNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Divya Sagar Narendra P. Singh Rashida Ginwala Xiaofang Huang Ramila Philip Mitzi Nagarkatti Prakash Nagarkatti Konstantin Neumann Jürgen Ruland Allison M. Andrews Servio H. Ramirez Zafar K. Khan Pooja Jain Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity
description	Abstract The mechanism of dendritic cells (DCs) recruitment across the blood brain barrier (BBB) during neuroinflammation has been the least explored amongst all leukocytes. For cells of myeloid origin, while integrins function at the level of adhesion, the importance of lectins remains unknown. Here, we identified functions of one C-type lectin receptor, CLEC12A, in facilitating DC binding and transmigration across the BBB in response to CCL2 chemotaxis. To test function of CLEC12A in an animal model of multiple sclerosis (MS), we administered blocking antibody to CLEC12A that significantly ameliorated disease scores in MOG35–55-induced progressive, as well as PLP138–151-induced relapsing-remitting experimental autoimmune encephalomyelitis (EAE) mice. The decline in both progression and relapse of EAE occurred as a result of reduced demyelination and myeloid cell infiltration into the CNS tissue. DC numbers were restored in the spleen of C57BL/6 and peripheral blood of SJL/J mice along with a decreased TH17 phenotype within CD4+ T-cells. The effects of CLEC12A blocking were further validated using CLEC12A knockout (KO) animals wherein EAE disease induction was delayed and reduced disease severity was observed. These studies reveal the utility of a DC-specific mechanism in designing new therapeutics for MS.
format	article
author	Divya Sagar Narendra P. Singh Rashida Ginwala Xiaofang Huang Ramila Philip Mitzi Nagarkatti Prakash Nagarkatti Konstantin Neumann Jürgen Ruland Allison M. Andrews Servio H. Ramirez Zafar K. Khan Pooja Jain
author_facet	Divya Sagar Narendra P. Singh Rashida Ginwala Xiaofang Huang Ramila Philip Mitzi Nagarkatti Prakash Nagarkatti Konstantin Neumann Jürgen Ruland Allison M. Andrews Servio H. Ramirez Zafar K. Khan Pooja Jain
author_sort	Divya Sagar
title	Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity
title_short	Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity
title_full	Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity
title_fullStr	Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity
title_full_unstemmed	Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity
title_sort	antibody blockade of clec12a delays eae onset and attenuates disease severity by impairing myeloid cell cns infiltration and restoring positive immunity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f3480ad339694c2197a255d3370edaa6
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Antibody blockade of CLEC12A delays EAE onset and attenuates disease severity by impairing myeloid cell CNS infiltration and restoring positive immunity

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