Adaptive Features of Natural Killer Cells in Multiple Sclerosis
Moreira Villanueva, Antía (Institut Hospital del Mar d'Investigacions Mèdiques)
Alari-Pahissa, Elvira (Universitat Pompeu Fabra)
Munteis, Elvira (Institut Hospital del Mar d'Investigacions Mèdiques)
Vera, Andrea (Institut Hospital del Mar d'Investigacions Mèdiques)
Zabalza, Ana (Institut Hospital del Mar d'Investigacions Mèdiques)
Llop, Mireia (Institut Hospital del Mar d'Investigacions Mèdiques)
Villarrubia, Noelia (Hospital Universitario Ramón y Cajal (Madrid))
Costa-Garcia, Marcel (Universitat Pompeu Fabra)
Alvarez-Lafuente, Roberto (Hospital Clínico San Carlos (Madrid))
Villar, Luisa Maria (Hospital Universitario Ramón y Cajal (Madrid))
López-Botet, Miguel (Institut Hospital del Mar d'Investigacions Mèdiques)
Martínez-Rodríguez, José E. (Institut Hospital del Mar d'Investigacions Mèdiques)
Universitat Autònoma de Barcelona

Data:	2019
Resum:	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(-) CD56 NK cells were found in HCMV(+) cases. However, PLZF(-) NK cells were detected uncoupled from other adaptive markers within the CD56 subset from HCMV(+) cases and among CD56 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(-) CD56 NK cells in HCMV(+) and increased PLZF(-) CD56 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.
Ajuts:	Ministerio de Economía y Competitividad FIS-PI17-00254 Ministerio de Economía y Competitividad SAF 2016-80363-C2-1-R
Nota:	Funding. This work was supported by 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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	FcεRIγ ; NKG2C ; PLZF ; Cytomegalovirus ; Multiple sclerosis ; Natural killer cells
Publicat a:	Frontiers in immunology, Vol. 10 (15 2019) , p. 2403, ISSN 1664-3224

DOI: 10.3389/fimmu.2019.02403
PMID: 31681293

12 p, 3.3 MB

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