The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to Inflammation

Innate lymphoid cells (ILCs) are tissue resident cells with organ-specific properties. Here, we show that the central nervous system (CNS) encompasses ILCs. In particular, CD3−NK1.1+ cells present in the murine CNS comprise natural killer (NK) cells, ILC1s, intermediate ILC1s (intILC1s) and ex-ILC3s...

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Main Authors: Silvina Romero-Suárez, Alba Del Rio Serrato, Roemel Jeusep Bueno, Daniel Brunotte-Strecker, Christina Stehle, Caio Andreeta Figueiredo, Laura Hertwig, Ildiko R. Dunay, Chiara Romagnani, Carmen Infante-Duarte
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-10-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.02337/full
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author Silvina Romero-Suárez
Alba Del Rio Serrato
Roemel Jeusep Bueno
Daniel Brunotte-Strecker
Christina Stehle
Caio Andreeta Figueiredo
Laura Hertwig
Laura Hertwig
Ildiko R. Dunay
Chiara Romagnani
Carmen Infante-Duarte
author_facet Silvina Romero-Suárez
Alba Del Rio Serrato
Roemel Jeusep Bueno
Daniel Brunotte-Strecker
Christina Stehle
Caio Andreeta Figueiredo
Laura Hertwig
Laura Hertwig
Ildiko R. Dunay
Chiara Romagnani
Carmen Infante-Duarte
author_sort Silvina Romero-Suárez
collection DOAJ
description Innate lymphoid cells (ILCs) are tissue resident cells with organ-specific properties. Here, we show that the central nervous system (CNS) encompasses ILCs. In particular, CD3−NK1.1+ cells present in the murine CNS comprise natural killer (NK) cells, ILC1s, intermediate ILC1s (intILC1s) and ex-ILC3s. We investigated the properties of CNS-ILC1s in comparison with CNS-NK cells during steady state and experimental autoimmune encephalomyelitis (EAE). ILC1s characteristically express CXCR3, CXCR6, DNAM-1, TRAIL, and CD200R and display heightened TNF-α production upon stimulation. In addition, ILC1s express perforin and are able to degranulate, although in a lesser extent than NK cells. Within the CNS compartments, ILC1s are enriched in the choroid plexus where very few NK cells are present, and also reside in the brain parenchyma and meninges. During EAE, ILC1s maintain stable IFN-γ and TNF-α levels while in NK cells the production of these cytokines increases as EAE progresses. Moreover, the amount of ILC1s and intILC1s increase in the parenchyma during EAE, but in contrast to NK cells, they show no signs of local proliferation. The upregulation in the inflamed brain of chemokines involved in ILC1 migration, such as CXCL9, CXCL10, and CXCL16 may lead to a recruitment of ILC1s from meninges or choroid plexus into the brain parenchyma. In sum, CNS-ILC1 phenotype, distribution and moderate inflammatory response during EAE suggest that they may act as gatekeepers involved in the control of neuroinflammation.
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spelling doaj.art-cffee1e659144451aed1172d0e8b298d2022-12-21T23:44:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02337472226The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to InflammationSilvina Romero-Suárez0Alba Del Rio Serrato1Roemel Jeusep Bueno2Daniel Brunotte-Strecker3Christina Stehle4Caio Andreeta Figueiredo5Laura Hertwig6Laura Hertwig7Ildiko R. Dunay8Chiara Romagnani9Carmen Infante-Duarte10Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute for Medical Immunology, Berlin, GermanyCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute for Medical Immunology, Berlin, GermanyCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute for Medical Immunology, Berlin, GermanyCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute for Medical Immunology, Berlin, GermanyInnate Immunity, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin, GermanyMedical Faculty, Institute of Inflammation and Neurodegeneration, Otto von Guericke University Magdeburg, Magdeburg, GermanyCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute for Medical Immunology, Berlin, GermanyDepartment of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenMedical Faculty, Institute of Inflammation and Neurodegeneration, Otto von Guericke University Magdeburg, Magdeburg, GermanyInnate Immunity, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin, GermanyCharité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institute for Medical Immunology, Berlin, GermanyInnate lymphoid cells (ILCs) are tissue resident cells with organ-specific properties. Here, we show that the central nervous system (CNS) encompasses ILCs. In particular, CD3−NK1.1+ cells present in the murine CNS comprise natural killer (NK) cells, ILC1s, intermediate ILC1s (intILC1s) and ex-ILC3s. We investigated the properties of CNS-ILC1s in comparison with CNS-NK cells during steady state and experimental autoimmune encephalomyelitis (EAE). ILC1s characteristically express CXCR3, CXCR6, DNAM-1, TRAIL, and CD200R and display heightened TNF-α production upon stimulation. In addition, ILC1s express perforin and are able to degranulate, although in a lesser extent than NK cells. Within the CNS compartments, ILC1s are enriched in the choroid plexus where very few NK cells are present, and also reside in the brain parenchyma and meninges. During EAE, ILC1s maintain stable IFN-γ and TNF-α levels while in NK cells the production of these cytokines increases as EAE progresses. Moreover, the amount of ILC1s and intILC1s increase in the parenchyma during EAE, but in contrast to NK cells, they show no signs of local proliferation. The upregulation in the inflamed brain of chemokines involved in ILC1 migration, such as CXCL9, CXCL10, and CXCL16 may lead to a recruitment of ILC1s from meninges or choroid plexus into the brain parenchyma. In sum, CNS-ILC1 phenotype, distribution and moderate inflammatory response during EAE suggest that they may act as gatekeepers involved in the control of neuroinflammation.https://www.frontiersin.org/article/10.3389/fimmu.2019.02337/fullinnate lymphoid cells (ILCs)ILC1snatural killer (NK) cellscentral nervous system (CNS)experimental autoimmune encephalomyelitis (EAE)mouse
spellingShingle Silvina Romero-Suárez
Alba Del Rio Serrato
Roemel Jeusep Bueno
Daniel Brunotte-Strecker
Christina Stehle
Caio Andreeta Figueiredo
Laura Hertwig
Laura Hertwig
Ildiko R. Dunay
Chiara Romagnani
Carmen Infante-Duarte
The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to Inflammation
Frontiers in Immunology
innate lymphoid cells (ILCs)
ILC1s
natural killer (NK) cells
central nervous system (CNS)
experimental autoimmune encephalomyelitis (EAE)
mouse
title The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to Inflammation
title_full The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to Inflammation
title_fullStr The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to Inflammation
title_full_unstemmed The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to Inflammation
title_short The Central Nervous System Contains ILC1s That Differ From NK Cells in the Response to Inflammation
title_sort central nervous system contains ilc1s that differ from nk cells in the response to inflammation
topic innate lymphoid cells (ILCs)
ILC1s
natural killer (NK) cells
central nervous system (CNS)
experimental autoimmune encephalomyelitis (EAE)
mouse
url https://www.frontiersin.org/article/10.3389/fimmu.2019.02337/full
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