{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:56:38Z","timestamp":1790736998938,"version":"4.1.0"},"reference-count":23,"publisher":"EDP Sciences","issue":"5","license":[{"start":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T00:00:00Z","timestamp":1558483200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med Sci (Paris)"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p>Le projet <jats:italic>Milieu Int\u00e9rieur<\/jats:italic> vise \u00e0 \u00e9lucider les facteurs environnementaux et h\u00e9r\u00e9ditaires qui fa\u00e7onnent un syst\u00e8me immunitaire sain, et \u00e0 d\u00e9finir ses fronti\u00e8res lors de l\u2019hom\u00e9ostasie et \u00e0 la suite d\u2019une stimulation immunitaire. Le projet repose sur un ph\u00e9notypage immunitaire de 1 000 donneurs sains. En corr\u00e9lant les mesures obtenues par analyse en cytom\u00e9trie en flux de la composition des cellules immunitaires du sang p\u00e9riph\u00e9rique en hom\u00e9ostasie avec les m\u00e9tadonn\u00e9es associ\u00e9es, nous avons d\u00e9fini des valeurs de r\u00e9f\u00e9rence de ph\u00e9notypes en fonction du sexe et de l\u2019\u00e2ge et constat\u00e9 un impact significatif du tabagisme et de l\u2019infection latente par le cytom\u00e9galovirus sur les ph\u00e9notypes mesur\u00e9s. Nous avons \u00e9galement identifi\u00e9 onze nouveaux polymorphismes (SNP, <jats:italic>single-nucleotide polymorphism<\/jats:italic>), associ\u00e9s \u00e0 des ph\u00e9notypes sp\u00e9cifiques de certaines cellules immunitaires. Des conduites exp\u00e9rimentales robustes et standardis\u00e9es ont \u00e9t\u00e9 \u00e9tablies pour quantifier les signatures prot\u00e9iques et transcriptionnelles de la r\u00e9ponse immunitaire r\u00e9sultant de la stimulation des cellules du sang p\u00e9riph\u00e9rique et pour explorer les d\u00e9terminants g\u00e9n\u00e9tiques et non-g\u00e9n\u00e9tiques de la variabilit\u00e9 de cette r\u00e9ponse. Les approches analytiques \u00e9tablies par <jats:italic>Milieu Int\u00e9rieur<\/jats:italic> et l\u2019ensemble des donn\u00e9es recueillies pourront ainsi servir de r\u00e9f\u00e9rence pour des \u00e9tudes comparatives avec diff\u00e9rentes maladies.<\/jats:p>","DOI":"10.1051\/medsci\/2019077","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T08:09:13Z","timestamp":1558512553000},"page":"423-430","source":"Crossref","is-referenced-by-count":2,"title":["Milieu Int\u00e9rieur"],"prefix":"10.1051","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0879-7099","authenticated-orcid":false,"given":"Milena","family":"Hasan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"250","published-online":{"date-parts":[[2019,5,22]]},"reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1016\/j.celrep.2016.10.053","volume":"17","author":"Aguirre-Gamboa","year":"2016","journal-title":"Cell Rep"},{"key":"R2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2014.12.020","volume":"160","author":"Brodin","year":"2015","journal-title":"Cell"},{"key":"R3","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cell.2013.08.041","volume":"155","author":"Orr\u00f9","year":"2013","journal-title":"Cell"},{"key":"R4","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.cell.2016.10.018","volume":"167","author":"Ter Horst","year":"2016","journal-title":"Cell"},{"key":"R5","doi-asserted-by":"crossref","first-page":"13850","DOI":"10.1038\/ncomms13850","volume":"8","author":"Mangino","year":"2017","journal-title":"Nat Commun"},{"key":"R6","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.cell.2018.06.045","volume":"174","author":"Olin","year":"2018","journal-title":"Cell"},{"key":"R7","doi-asserted-by":"crossref","first-page":"4684","DOI":"10.1038\/ncomms5684","volume":"5","author":"Enroth","year":"2014","journal-title":"Nat Commun"},{"key":"R8","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.celrep.2018.09.021","volume":"25","author":"Zalocusky","year":"2018","journal-title":"Cell Rep"},{"key":"R9","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/ni.3371","volume":"17","author":"Carr","year":"2016","journal-title":"Nat Immunol"},{"key":"R10","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.cell.2015.02.046","volume":"161","author":"Roederer","year":"2015","journal-title":"Cell"},{"key":"R11","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.clim.2014.12.004","volume":"157","author":"Thomas","year":"2015","journal-title":"Clin Immunol"},{"key":"R12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41590-018-0049-7","volume":"19","author":"Patin","year":"2018","journal-title":"Nat Immunol"},{"key":"R13","doi-asserted-by":"crossref","first-page":"eaao2966","DOI":"10.1126\/scitranslmed.aao2966","volume":"10","author":"Clave","year":"2018","journal-title":"Sci Transl Med"},{"key":"R14","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.immuni.2014.03.002","volume":"40","author":"Duffy","year":"2014","journal-title":"Immunity"},{"key":"R15","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1016\/j.celrep.2016.08.011","volume":"16","author":"Urrutia","year":"2016","journal-title":"Cell Rep"},{"key":"R16","doi-asserted-by":"crossref","first-page":"E488","DOI":"10.1073\/pnas.1714765115","volume":"115","author":"Piasecka","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"R17","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/ng.2424","volume":"44","author":"Xu","year":"2012","journal-title":"Nat Genet"},{"key":"R18","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.cell.2016.09.024","volume":"167","author":"Quach","year":"2016","journal-title":"Cell"},{"key":"R19","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.clim.2014.12.008","volume":"157","author":"Hasan","year":"2015","journal-title":"Clin Immunol"},{"key":"R20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.clim.2014.12.009","volume":"157","author":"Chen","year":"2015","journal-title":"Clin Immunol"},{"key":"R21","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.clim.2017.09.019","volume":"183","author":"Duffy","year":"2017","journal-title":"Clin Immunol"},{"key":"R22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13073-018-0568-8","volume":"10","author":"Scepanovic","year":"2018","journal-title":"Genome Med"},{"key":"R23","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1051\/medsci\/2019069","volume":"35","author":"Duffy","year":"2019","journal-title":"Med Sci (Paris)"}],"container-title":["m\u00e9decine\/sciences"],"original-title":[],"link":[{"URL":"https:\/\/www.medecinesciences.org\/10.1051\/medsci\/2019077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T12:13:26Z","timestamp":1602850406000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.medecinesciences.org\/10.1051\/medsci\/2019077"}},"subtitle":["Comprendre l\u2019h\u00e9t\u00e9rog\u00e9n\u00e9it\u00e9 du syst\u00e8me immunitaire sain pour avancer sur la voie de la m\u00e9decine personnalis\u00e9e"],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":23,"journal-issue":{"issue":"5"},"alternative-id":["msc180288"],"URL":"https:\/\/doi.org\/10.1051\/medsci\/2019077","relation":{},"ISSN":["0767-0974","1958-5381"],"issn-type":[{"value":"0767-0974","type":"print"},{"value":"1958-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5]]}}}