dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Carrión, Belinda |
dc.contributor.author | Liu, Yawei |
dc.contributor.author | Hadi, Mahdieh |
dc.contributor.author | Lundstrom, Jon |
dc.contributor.author | Christensen, Jeppe Romme |
dc.contributor.author | Ammitzbøll, Cecilie |
dc.contributor.author | Montalban Gairín, Xavier |
dc.contributor.author | Comabella Lopez, Manuel |
dc.date.accessioned | 2022-04-22T13:25:35Z |
dc.date.available | 2022-04-22T13:25:35Z |
dc.date.issued | 2021-11 |
dc.identifier.citation | Carrión B, Liu Y, Hadi M, Lundstrom J, Christensen JR, Ammitzbøll C, et al. Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021 Nov;8(6):e1065. |
dc.identifier.issn | 2332-7812 |
dc.identifier.uri | https://hdl.handle.net/11351/7381 |
dc.description | Progressive Multiple Sclerosis; T Cells |
dc.description.abstract | Background and Objective The aim of this study was to determine whether natural killer T (NKT) cells, including invariant (i) NKT cells, have clinical value in preventing the progression of multiple sclerosis (MS) by examining the mechanisms by which a distinct self-peptide induces a novel, protective invariant natural killer T cell (iNKT cell) subset.
Methods We performed a transcriptomic and functional analysis of iNKT cells that were reactive to a human collagen type II self-peptide, hCII707-721, measuring differentially induced genes, cytokines, and suppressive capacity.
Results We report the first transcriptomic profile of human conventional vs novel hCII707-721–reactive iNKT cells. We determined that hCII707-721 induces protective iNKT cells that are found in the blood of healthy individuals but not progressive patients with MS (PMS). By transcriptomic analysis, we observed that hCII707-721 promotes their development and proliferation, favoring the splicing of full-length AKT serine/threonine kinase 1 (AKT1) and effector function of this unique lineage by upregulating tumor necrosis factor (TNF)-related genes. Furthermore, hCII707-721–reactive iNKT cells did not upregulate interferon (IFN)-γ, interleukin (IL)-4, IL-10, IL-13, or IL-17 by RNA-seq or at the protein level, unlike the response to the glycolipid alpha-galactosylceramide. hCII707-721–reactive iNKT cells increased TNFα only at the protein level and suppressed autologous-activated T cells through FAS-FAS ligand (FAS-FASL) and TNFα-TNF receptor I signaling but not TNF receptor II.
Discussion Based on their immunomodulatory properties, NKT cells have a potential value in the treatment of autoimmune diseases, such as MS. These significant findings suggest that endogenous peptide ligands can be used to expand iNKT cells, without causing a cytokine storm, constituting a potential immunotherapy for autoimmune conditions, including PMS. |
dc.language.iso | eng |
dc.publisher | Lippincott Williams & Wilkins |
dc.relation.ispartofseries | Neurology - Neuroimmunology Neuroinflammation;8(6) |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.source | Scientia |
dc.subject | Esclerosi múltiple - Tractament |
dc.subject | Cèl·lules K - Fisiologia |
dc.subject | Medicaments immunosupressors |
dc.subject.mesh | Multiple Sclerosis, Chronic Progressive |
dc.subject.mesh | Natural Killer T-Cells |
dc.subject.mesh | /physiology |
dc.subject.mesh | Immunosuppressive Agents |
dc.title | Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1212/NXI.0000000000001065 |
dc.subject.decs | esclerosis múltiple crónica progresiva |
dc.subject.decs | células T asesinas naturales |
dc.subject.decs | /fisiología |
dc.subject.decs | inmunosupresores |
dc.relation.publishversion | https://doi.org/10.1212/NXI.0000000000001065 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Carrión B, Liu Y, Hadi M, Lundstrom J] Biotech Research and Innovation Centre (BRIC), University of Copenhagen. [Christensen JR, Ammitzbøll C] Danish Multiple Sclerosis Center, University of Copenhagen and Department of Neurology, Rigshospitalet. [Comabella M, Montalban X] Unitat de Neuroimmunologia Clínica, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain |
dc.identifier.pmid | 34385365 |
dc.identifier.wos | 000712132000034 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |