{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:33:39Z","timestamp":1791462819606,"version":"4.3.4"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T00:00:00Z","timestamp":1652400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CNRS"},{"name":"Agence Nationale pour la Recherche","award":["CE14-14066"],"award-info":[{"award-number":["CE14-14066"]}]},{"name":"Agence Nationale pour la Recherche","award":["CE17-0014"],"award-info":[{"award-number":["CE17-0014"]}]},{"DOI":"10.13039\/501100004718","name":"Toulouse University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004718","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Narcolepsy with cataplexy or narcolepsy type 1 is a disabling chronic sleep disorder resulting from the destruction of orexinergic neurons in the hypothalamus. The tight association of narcolepsy with HLA-DQB1*06:02 strongly suggest an autoimmune origin to this disease. Furthermore, converging epidemiological studies have identified an increased incidence for narcolepsy in Europe following Pandemrix\u00ae vaccination against the 2009\u20132010 pandemic \u2018influenza\u2019 virus strain. The potential immunological link between the Pandemrix\u00ae vaccination and narcolepsy remains, however, unknown. Deciphering these mechanisms may reveal pathways potentially at play in most cases of narcolepsy.<\/jats:p>\n               <jats:p>Here, we developed a mouse model allowing to track and study the T-cell response against \u2018influenza\u2019 virus haemagglutinin, which was selectively expressed in the orexinergic neurons as a new self-antigen. Pandemrix\u00ae vaccination in this mouse model resulted in hypothalamic inflammation and selective destruction of orexin-producing neurons. Further investigations on the relative contribution of T-cell subsets in this process revealed that haemagglutinin-specific CD4 T cells were necessary for the development of hypothalamic inflammation, but insufficient for killing orexinergic neurons. Conversely, haemagglutinin-specific CD8 T cells could not initiate inflammation but were the effectors of the destruction of orexinergic neurons. Additional studies revealed pathways potentially involved in the disease process. Notably, the interferon-\u03b3 pathway was proven essential, as interferon-\u03b3-deficient CD8 T cells were unable to elicit the loss of orexinergic neurons.<\/jats:p>\n               <jats:p>Our work demonstrates that an immunopathological process mimicking narcolepsy can be elicited by immune cross-reactivity between a vaccine antigen and a neuronal self-antigen. This process relies on a synergy between autoreactive CD4 and CD8 T cells for disease development. This work furthers our understanding of the mechanisms and pathways potentially involved in the development of a neurological side effect due to a vaccine and, likely, to narcolepsy in general.<\/jats:p>","DOI":"10.1093\/brain\/awab455","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T20:16:42Z","timestamp":1639426602000},"page":"2018-2030","source":"Crossref","is-referenced-by-count":35,"title":["Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7447-344X","authenticated-orcid":false,"given":"Rapha\u00ebl","family":"Bernard-Valnet","sequence":"first","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS , Toulouse , France"},{"name":"Service of Neurology, Clinical Neurosciences Department, Lausanne University Hospital and Lausanne University , Lausanne , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Frieser","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS , Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan Hung","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS , Toulouse , France"},{"name":"Vinmec Institute of Applied Science and Regenerative Medicine, Vinmec Healthcare System , Hanoi , Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Khajavi","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS , Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9mence","family":"Qu\u00e9riault","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS , Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Arthaud","sequence":"additional","affiliation":[{"name":"INSERM U1028, CNRS UMR 5292, Center for Research in Neuroscience, University of Lyon 1 , Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Melzi","sequence":"additional","affiliation":[{"name":"INSERM U1028, CNRS UMR 5292, Center for Research in Neuroscience, University of Lyon 1 , Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Fusade-Boyer","sequence":"additional","affiliation":[{"name":"IHAP, UMR1225, Universit\u00e9 de Toulouse, INRAe, ENVT , Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Masson","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS , Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Zytnicki","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Math\u00e9matiques et Informatique Appliqu\u00e9es, INRAE , Castanet-Tolosan , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhadi","family":"Saoudi","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS , Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Dauvilliers","sequence":"additional","affiliation":[{"name":"National Reference Center for Orphan Diseases, Narcolepsy, Idiopathic hypersomnia and Kleine-Levin Syndrome, Department of Neurology, Gui-de-Chauliac Hospital, CHU de Montpellier, INSERM U1061 , Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Peyron","sequence":"additional","affiliation":[{"name":"INSERM U1028, CNRS UMR 5292, Center for Research in Neuroscience, University of Lyon 1 , Bron , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Bauer","sequence":"additional","affiliation":[{"name":"Center for Brain Research, Medical University of Vienna , Vienna , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-5475","authenticated-orcid":false,"given":"Roland S","family":"Liblau","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS , Toulouse , France"},{"name":"Department of Immunology, Toulouse University Hospitals , Toulouse , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"issue":"27","key":"2022091207501028400_awab455-B1","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1056\/NEJMra1500587","article-title":"Narcolepsy","volume":"373","author":"Scammell","year":"2015","journal-title":"N Engl J Med"},{"issue":"9","key":"2022091207501028400_awab455-B2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41582-019-0226-9","article-title":"Narcolepsy\u2014clinical spectrum, aetiopathophysiology, diagnosis and treatment","volume":"15","author":"Bassetti","year":"2019","journal-title":"Nat Rev Neurol"},{"issue":"9","key":"2022091207501028400_awab455-B3","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/79690","article-title":"A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human 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