The immunopathogenesis of narcolepsy type 1

Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt

Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing. Increased T cell reactivity against HCRT has been consistently reported in patients with NT1, but data demonstrating a primary role for T cells in neuronal destruction are currently lacking. Animal models are providing clues regarding the roles of autoreactive CD4+ and CD8+ T cells in the disease. Elucidation of the pathogenesis of NT1 will allow for the development of targeted immunotherapies at disease onset and could serve as a model for other immune-mediated neurological diseases.
OriginalsprogEngelsk
TidsskriftNature Reviews Immunology
Vol/bind24
Sider (fra-til)33-48
ISSN1474-1733
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
The authors thank L. Chatenoud, R. Mallone and D. Dunia for their feedback on the manuscript, and T. Sarkanen and D. Frieser for their help with Supplementary Fig. and Supplementary Fig. , respectively. R.S.L. is supported by Institut Universitaire de France and grants from Fondation pour la Recherche Médicale, the Agence Nationale de la Recherche (BETPSY RHU consortium, NARCOMICS consortium and ANR-18-CE17-0014-03). Y.D. is supported by grants from Agence Nationale de la Recherche (NARCOMICS consortium and ANR-18-CE17-0014-03). D.L. is supported by a PRIMA grant from the Swiss National Science Foundation (PR00P3_185742). B.R.K. is supported by the Lundbeck Foundation (grant R344-2020-749), and a Carlsberg Foundation Young Researcher Fellowship. E.J.M.’s research on narcolepsy is supported by National Institutes of Health grant R01 AI144798.

Funding Information:
R.S.L. has received grant support from GlaxoSmithKline and Roche and has consulted for Merck, Novartis, Biogen and Sanofi-Genzyme. B.R.K. has consulted for UCB Pharma, Lundbeck, Gubra and Orexia Therapeutics, has submitted patent applications within the field of narcolepsy and is a founder of the University of Copenhagen spin-out company Ceremedy ApS. Y.D. is a consultant for and has participated in advisory boards for Jazz Pharmaceuticals, UCB Pharma, Avadel, Idorsia, Orexia, Takeda and Bioprojet. In the last 3 years, E.J.M. received grant support from, is a consultant for or has participated in advisory boards for Apple, Avadel, Axsome, Huami, Harmony, Idorsia, Jazz Pharmaceuticals, Orexia/Centessa, Sunovion and Takeda. D.L. declares no competing interests.

Publisher Copyright:
© 2023, Springer Nature Limited.

ID: 360030070