https://m2.mtmt.hu/ eng 2026-05-31 15:57 JournalArticle 32636201 VALIDATED true Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Budapest, Hungary Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Doctoral School of Molecular Cellular and Immune Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary Software Engineering Institute, John von Neumann Faculty of Informatics, Óbuda University, Budapest, Hungary University Hospital Jena, Friedrich Schiller University, Jena, Germany Molecular and Integrative Biosciences and Neuroscience Center (HiLIFE), University of Helsinki, Helsinki, Finland Export Date: 24 February 2022 CODEN: PBLIB Correspondence Address: Dénes, Á.; Momentum Laboratory of Neuroimmunology, Hungary; email: denes.adam@koki.hu Chemicals/CAS: bumetanide, 28395-03-1 Funding details: BO/00558/19/5, K131844, NKP-20 3-II, NKP-21-5, bolyai-janos-kutatasi-osztondij-105319 Funding details: Deutsche Forschungsgemeinschaft, DFG, SPP 1665 Funding details: Academy of Finland, AKA Funding details: Bundesministerium für Bildung und Forschung, BMBF Funding details: Magyar Tudományos Akadémia, MTA, 2019-2.1.7-ERA-NET-2020-00004, ERC-CoG 724994, LP2016-4/2016 Funding details: Sigrid Juséliuksen Säätiö Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding details: Neuron Nadační Fond Na Podporu Vědy, Neuron, ACRoBAT 01EW1706 Funding details: Magyarország Kormánya Funding text 1: This work was supported by ?Momentum? research grant from the Hungarian Academy of Sciences (LP2016-4/2016 to A.D.; https://mta.hu/lendulet) and ERC-CoG 724994 (to A.D.; https://erc.europa.eu/), with contribution from 2019-2.1.7-ERA-NET-2020-00004 (https://nkfih. gov.hu). Additionally, this work was funded by Hungarian National Scientific Research Fund (NKFIH-OTKA Grant No. K131844 to S.B.), the J?nos Bolyai Research Scholarship of the Hungarian Academy of Sciences (to C.C. and N.L., BO/00558/19/5; https://mta.hu/bolyai-osztondij/ bolyai-janos-kutatasi-osztondij-105319), ?NKP-20 3-II (to B.P.) and ?NKP-21-5 (to C.C. and N.L.; http://www.unkp.gov.hu/unkp-rol) of the New National Excellence Program of the Ministry for Innovation and Technology, Hungary; German Research Foundation (SPP 1665; https://www.dfg. de/en/) and the Federal Ministry of Education and Research (NEURON ACRoBAT 01EW1706) to C.A. H.; and the Academy of Finland and Sigrid Jus?lius Foundation to K.K.. Prepared with the professional support of the Doctoral Scholarship Program of th Cooperative Doctoral Program of the Ministry of Innovation and Technology Financed from The National Research, Development and Innovation Fund (to B.P.). A.A. holds a Stipendium Hungaricum Scholarship from the Government of Hungary (https://stipendiumhungaricum.hu/). K. K.?s work was supported by the Academy of Finland and by the Sigrid Jus?lius Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank J?nos Szabadics for his valuable remarks on the electrophysiology part of the manuscript; L?szl? Barna and the Nikon Imaging Center at the Institute of Experimental Medicine for kindly providing microscopy support; D?ra Gali-Gy?rkei for her excellent technical assistance; and the Cell Biology Center at the Institute of Experimental Medicine. 0 false 2026-05-21T13:55:17.471+0000 2026-04-16T12:45:33.363+0000 2022-01-31T14:15:59.546+0000 true 10049757 Jász Anikó /api/admin/10049757 Admin true 10049757 2026-05-20T13:09:18.317+0000 2026-05-20T13:09:18.317+0000 2022-02-23T08:36:46.623+0000 true 10015207 Tamássyné T. Zsuzsa /api/admin/10015207 Admin true 10015207 2022-03-02T07:46:35.502+0000 true 10080205 Szalóky-Siki Ágnes /api/admin/10080205 Admin true Admin 10067876 /api/admin/10067876 Ladányi Gusztáv true true Admin 10080106 /api/admin/10080106 Király Magdolna true true 2024-10-17T16:46:05.635+0000 true false true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType 101 true 10000059 true 1 /api/category/1 Category true 1 Tóth, Krisztina The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner true true /api/journal/10001349 REVIEWED true false 10001349 false 10001349 true 1544-9173 1545-7885 Journal FOREIGN 20 1 e3001526 e3001526 31 2022 The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1β (IL-1β), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema, and, worse, neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders. 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Krisztina (<span class="authorship-author-name">Tóth Krisztina</span> <span class="authorAux-mtmt"> Idegtudományok</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Neuroimmunology; <span title="Semmelweis University">SU</span>/School of PhD Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10030597"><a href="/gui2/?type=authors&mode=browse&sel=10030597" target="_blank">Lénárt Nikolett (<span class="authorship-author-name">Lénárt Nikolett</span> <span class="authorAux-mtmt"> neurobiológia</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Neuroimmunology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10078045"><a href="/gui2/?type=authors&mode=browse&sel=10078045" target="_blank">Berki Péter (<span class="authorship-author-name">Berki Péter</span> <span class="authorAux-mtmt"> neurobiológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/School of PhD Studies; <span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Cerebral Cortex Research</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10049451"><a href="/gui2/?type=authors&mode=browse&sel=10049451" target="_blank">Fekete Rebeka (<span class="authorship-author-name">Fekete Rebeka</span> <span class="authorAux-mtmt"> idegtudomány</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Neuroimmunology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="173"><a href="/gui2/?type=authors&mode=browse&sel=173" target="_blank">Szabadits Eszter (<span class="authorship-author-name">Cserépné Szabadits Eszter</span> <span class="authorAux-mtmt"> Idegtudomány</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Neuroimmunology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10061174"><a href="/gui2/?type=authors&mode=browse&sel=10061174" target="_blank">Pósfai Balázs (<span class="authorship-author-name">Pósfai Balázs</span> <span class="authorAux-mtmt"> Idegtudomány</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Neuroimmunology; <span title="Semmelweis University">SU</span>/School of PhD Studies</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="172"><a href="/gui2/?type=authors&mode=browse&sel=172" target="_blank">Cserép Csaba (<span class="authorship-author-name">Cserép Csaba</span> <span class="authorAux-mtmt"> Idegtudomány, Neurobiológia</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Neuroimmunology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10098141"><a href="/gui2/?type=authors&mode=browse&sel=10098141" target="_blank">Alatshan Ahmad (<span class="authorship-author-name">Alatshan Ahmad</span> <span class="authorAux-mtmt"> Immunology</span>) </a> </span> <span class="author-affil"><span title="University of Debrecen">UD</span>/<span title="Faculty of Medicine">Faculty of Medicine</span>/Department of Physiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10020759"><a href="/gui2/?type=authors&mode=browse&sel=10020759" target="_blank">Benkő Szilvia (<span class="authorship-author-name">Benkő Szilvia</span> <span class="authorAux-mtmt"> Immunológia</span>) </a> </span> <span class="author-affil"><span title="University of Debrecen">UD</span>/<span title="Faculty of Medicine">Faculty of Medicine</span>/Department of Physiology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10052161"><a href="/gui2/?type=authors&mode=browse&sel=10052161" target="_blank">Kiss Dániel (<span class="authorship-author-name">Kiss Dániel</span> <span class="authorAux-mtmt"> számítógépes biológia</span>) </a> </span> <span class="author-affil"><span title="Óbuda University">ÓU</span>/<span title="Neumann János Faculty of Informatics">NJFCS</span>/Szoftvertervezés- és Fejlesztés Intézet</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Hübner Christian A. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10009114"><a href="/gui2/?type=authors&mode=browse&sel=10009114" target="_blank">Gulyás Attila (<span class="authorship-author-name">Gulyás Attila</span> <span class="authorAux-mtmt"> Neurobiológia</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Cerebral Cortex Research</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kaila Kai </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10011503"><a href="/gui2/?type=authors&mode=browse&sel=10011503" target="_blank">Környei Zsuzsanna (<span class="authorship-author-name">Környei Zsuzsanna</span> <span class="authorAux-mtmt"> Neuroimmunológia; Idegi sejt- és fejlődésbiológia</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Neuroimmunology</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10012934"><a href="/gui2/?type=authors&mode=browse&sel=10012934" target="_blank">Dénes Ádám ✉ (<span class="authorship-author-name">Dénes Ádám</span> <span class="authorAux-mtmt"> Neurobiológia, neuroimmunológia</span>) </a> </span> <span class="author-affil"><span title="Institute of Experimental Medicine">IEM</span>/Laboratory of Neuroimmunology</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32636201" target="_blank">The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner</a></div> <div> <span class="journal-title">PLOS BIOLOGY</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1544-9173">1544-9173</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1545-7885">1545-7885</a>)</span>: <span class="journal-volume">20</span> <span class="journal-issue">1</span> <span class="page"> Paper e3001526. 31 p. </span> <span class="year">(2022)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1371/journal.pbio.3001526" target="_blank" href="https://doi.org/10.1371/journal.pbio.3001526"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000748720800001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000748720800001"> WoS </a> </span> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:black" title="149669" target="_blank" href="http://real.mtak.hu/149669"> REAL </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85123845441" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85123845441"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="35085235" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=35085235&dopt=Abstract"> PubMed </a> </span> <span class="id identifier oa_NONE" title=" None "> <a style="color:blue" title="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123845441&doi=10.1371%2fjournal.pbio.3001526&partnerID=40&md5=a99c86684d39e6a29ce6397b8656de7f" target="_blank" href="https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123845441&doi=10.1371%2fjournal.pbio.3001526&partnerID=40&md5=a99c86684d39e6a29ce6397b8656de7f"> Other URL </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Agricultural and Biological Sciences (miscellaneous)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Biochemistry, Genetics and Molecular Biology (miscellaneous)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Immunology and Microbiology (miscellaneous)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> <div class="journal-subject">Journal subject: Scopus - Neuroscience (miscellaneous)&nbsp;&nbsp;&nbsp;Rank:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 34</span> | Independent citation: 30 | Self citation: 4 | Unknown citation: 0 | Number of citations in WoS: 32 | Number of citations in Scopus:&nbsp;28 | WoS/Scopus assigned:&nbsp;33 | Number of citations with DOI:&nbsp;34 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32636201&sort=publishedYear,desc&sort=title"> Number of cited publications: 10 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 32636201</span> | <span class="status-data status-VALIDATED"> Validated </span> Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">kézi felvitel</span> </div> <div class="funder"> (LP2016-4/2016) Funder: MTA, (ERC-CoG 724994) Funder: ERC, (2019-2.1.7-ERA-NET-2020-00004) Funder: MIT, A mintázatfelismerő Nod-like receptorok, mint új, potenciális szabályozók a vázizom regeneráció m...(K131844) Funder: HSRF, János Bolyai Research Scholarship of the Hungarian Academy of Science(BO/00558/19), Új Nemzeti Kiválóság Program, Felsőoktatási Doktori Hallgatói Kutatói Ösztöndíj(ÚNKP-20-3-II) Funder: MIT, Új Nemzeti Kiválóság Program, Bolyai+ Felsőoktatási Fiatal Oktatói, Kutatói Ösztöndíj(ÚNKP-21-5) Funder: MIT, Resolving and manipulating neuronal networks in the mammalian brain - from correlative to causal ...(SPP 1665) Funder: DFG, Veränderte Chlorid-Homöostase nach Hirnverletzungen(NEURON ACROBAT 01EW1706) Funder: BMBF, Stipendium Hungaricum Scholarship(Stipendium) Funder: Tempus P. F. </div> <div class="lastModified">Last Modified: 2026.04.16. 14:45 Zsuzsa Ágnes Vida (DE/ÁOK/ElettI Admin 5, admin) </div> <div class="lockedBy">Centrally managed 2024.10.17. 18:46 Gusztáv Ladányi (MTMT API user, admin) Magdolna Király (MTMT ellenőrzés admin5) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Comments</u>: Momentum Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Budapest, Hungary Department of Physiology, Faculty of Medici...</pre> </div></div>