Adaptive features of natural killer cells in multiple sclerosis

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• dc.contributor.author Moreira Villanueva, Antía
• dc.contributor.author Alari-Pahissa, Elisenda
• dc.contributor.author Munteis Olivas, Elvira
• dc.contributor.author Vera, Andrea
• dc.contributor.author Zabalza, Ana
• dc.contributor.author Llop, Mireia
• dc.contributor.author Villarrubia, Noelia
• dc.contributor.author Costa García, Marcel, 1989-
• dc.contributor.author Álvarez-Lafuente, Roberto
• dc.contributor.author Villar, Luisa Maria
• dc.contributor.author López-Botet, M. (Miguel)
• dc.contributor.author Martínez-Rodriguez, José E.
• dc.date.accessioned 2019-12-13T08:33:46Z
• dc.date.available 2019-12-13T08:33:46Z
• dc.date.issued 2019
• dc.description.abstract Human cytomegalovirus (HCMV) has been recently related with a lower susceptibility to multiple sclerosis (MS). HCMV promotes an adaptive development of NK cells bearing the CD94/NKG2C receptor with a characteristic phenotypic and functional profile. NK cells are proposed to play an immunoregulatory role in MS, and expansion of the NKG2C(+) subset was recently associated with reduced disability progression. To further explore this issue, additional adaptive NK cell markers, i.e., downregulation of FcεRIγ chain (FcRγ) and PLZF transcription factor, as well as antibody-dependent NK cell activation were assessed in controls and MS patients considering HCMV serology and clinical features. In line with previous reports, increased proportions of NKG2C(+), FcRγ(-), and PLZF(-) CD56dim NK cells were found in HCMV(+) cases. However, PLZF(-) NK cells were detected uncoupled from other adaptive markers within the CD56bright subset from HCMV(+) cases and among CD56dim NK cells from HCMV(-) MS patients, suggesting an additional effect of HCMV-independent factors in PLZF downregulation. Interferon-β therapy was associated with lower proportions of FcRγ(-) CD56dim NK cells in HCMV(+) and increased PLZF(-) CD56bright NK cells in HCMV(-) patients, pointing out to an influence of the cytokine on the expression of adaptive NK cell-associated markers. In addition, proportions of NKG2C(+) and FcRγ(-) NK cells differed in progressive MS patients as compared to controls and other clinical forms. Remarkably, an adaptive NK cell phenotype did not directly correlate with enhanced antibody-triggered degranulation and TNFα production in MS in contrast to controls. Altogether, our results provide novel insights into the putative influence of HCMV and adaptive NK cells in MS.
• dc.description.sponsorship This work was supported by grants FIS/PI17/00254, SAF 2016-80363-C2-1-R (Spanish Ministry of Economy and Competitiveness and FEDER), the EU FP7-MINECO Infect-ERA Program (PCIN-2015-191-C02-01), and Red Española de Esclerosis Múltiple (REEM) from the Instituto de Salud Carlos III, the European Regional Development Fund (Grant RD16/0015/0011), and the Spanish Ministry of Economy and Competitiveness.
• dc.format.mimetype application/pdf
• dc.identifier.citation Moreira A, Alari-Pahissa E, Munteis E, Vera A, Zabalza A, Llop M et al. Adaptive features of natural killer cells in multiple sclerosis. Front Immunol. 2019;10:2403. DOI: 10.3389/fimmu.2019.02403
• dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2019.02403
• dc.identifier.issn 1664-3224
• dc.identifier.uri http://hdl.handle.net/10230/43161
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Frontiers in Immunology. 2019;10:2403
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80363-C2-1-R
• dc.rights © 2019 Moreira, Alari-Pahissa, Munteis, Vera, Zabalza, Llop, Villarrubia, Costa-García, Álvarez-Lafuente, Villar, López-Botet and Martínez-Rodríguez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword FcεRIγ
• dc.subject.keyword NKG2C
• dc.subject.keyword PLZF
• dc.subject.keyword Cytomegalovirus
• dc.subject.keyword Multiple sclerosis
• dc.subject.keyword Natural killer cells
• dc.title Adaptive features of natural killer cells in multiple sclerosis
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion