Specific and Polyfunctional T Cell Response Against <i>N</i>-Methyl-<span style="font-variant: small-caps">d</span>-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model
Background: Anti-<i>N</i>-Methyl-<span style="font-variant: small-caps;">d</span>-aspartate receptor (NMDAR) autoimmune encephalitis (NMDAR AE) is an autoimmune disease characterized by severe psychiatric and neurological symptoms. While the pathogenic role of antib...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/11/2458 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850145691402240000 |
|---|---|
| author | Léonie Lesec Julien Serrier Célia Seillier Benoit Bernay Caroline Regnauld Jonathane Furon Jérôme Leprince Benjamin Lefranc Denis Vivien Fabian Docagne Brigitte Le Mauff Olivier Toutirais |
| author_facet | Léonie Lesec Julien Serrier Célia Seillier Benoit Bernay Caroline Regnauld Jonathane Furon Jérôme Leprince Benjamin Lefranc Denis Vivien Fabian Docagne Brigitte Le Mauff Olivier Toutirais |
| author_sort | Léonie Lesec |
| collection | DOAJ |
| description | Background: Anti-<i>N</i>-Methyl-<span style="font-variant: small-caps;">d</span>-aspartate receptor (NMDAR) autoimmune encephalitis (NMDAR AE) is an autoimmune disease characterized by severe psychiatric and neurological symptoms. While the pathogenic role of antibodies (Abs) directed against the GluN1 subunit of NMDAR is well described in this disease, the immune mechanisms involved in the generation of the autoimmune B cell response, especially the role of T helper cells, are poorly understood. Previously, we developed a B-cell-mediated mouse model of NMDAR AE by immunization with a GluN1<sub>359–378</sub> peptide that drives a series of symptoms that recapitulate AE such as anxiety behaviour and spatial memory impairment. Results: In this mouse model, we identified anti-GluN1-specific CD4<sup>+</sup> but also CD8<sup>+</sup> T cells in both spleen and meninges. T helper cells have a polyfunctional profile, arguing for a T and B cell crosstalk to generate anti-GluN1 pathogenic Abs. Interestingly, proteomic analysis of AE meninges showed enrichment of differentially expressed proteins in biological processes associated with B cell activation and cytokine signalling pathways. Conclusions: This study identified, for the first time, a potential contribution of T helper cells in the pathology of NMDAR AE and paved the way for the development of future tolerogenic approaches to treat relapses. |
| format | Article |
| id | doaj-art-caefd0070d7143d19a7926402f910949 |
| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-caefd0070d7143d19a7926402f9109492025-08-20T02:28:02ZengMDPI AGBiomedicines2227-90592024-10-011211245810.3390/biomedicines12112458Specific and Polyfunctional T Cell Response Against <i>N</i>-Methyl-<span style="font-variant: small-caps">d</span>-aspartate Receptor in an Autoantibody-Mediated Encephalitis ModelLéonie Lesec0Julien Serrier1Célia Seillier2Benoit Bernay3Caroline Regnauld4Jonathane Furon5Jérôme Leprince6Benjamin Lefranc7Denis Vivien8Fabian Docagne9Brigitte Le Mauff10Olivier Toutirais11Normandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceNormandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceNormandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceNormandie Univ, UNICAEN, US EMerode, Plateform Proteogen, 14000 Caen, FranceNormandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceNormandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceNormandie Univ, UNIROUEN, INSERM, U1239 NorDiC, Neuronal and Neuroendocrine Differentiation and Communication, 76000 Rouen, FranceNormandie Univ, UNIROUEN, INSERM, US51 HeRacLeS, PRIMACEN, 76000 Rouen, FranceNormandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceNormandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceNormandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceNormandie Univ, UNICAEN, INSERM, GIP Cyceron, Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), 14032 Caen, FranceBackground: Anti-<i>N</i>-Methyl-<span style="font-variant: small-caps;">d</span>-aspartate receptor (NMDAR) autoimmune encephalitis (NMDAR AE) is an autoimmune disease characterized by severe psychiatric and neurological symptoms. While the pathogenic role of antibodies (Abs) directed against the GluN1 subunit of NMDAR is well described in this disease, the immune mechanisms involved in the generation of the autoimmune B cell response, especially the role of T helper cells, are poorly understood. Previously, we developed a B-cell-mediated mouse model of NMDAR AE by immunization with a GluN1<sub>359–378</sub> peptide that drives a series of symptoms that recapitulate AE such as anxiety behaviour and spatial memory impairment. Results: In this mouse model, we identified anti-GluN1-specific CD4<sup>+</sup> but also CD8<sup>+</sup> T cells in both spleen and meninges. T helper cells have a polyfunctional profile, arguing for a T and B cell crosstalk to generate anti-GluN1 pathogenic Abs. Interestingly, proteomic analysis of AE meninges showed enrichment of differentially expressed proteins in biological processes associated with B cell activation and cytokine signalling pathways. Conclusions: This study identified, for the first time, a potential contribution of T helper cells in the pathology of NMDAR AE and paved the way for the development of future tolerogenic approaches to treat relapses.https://www.mdpi.com/2227-9059/12/11/2458autoimmune encephalitis<i>N</i>-methyl-<span style="font-variant: small-caps">d</span>-aspartate receptorT cellsB cells |
| spellingShingle | Léonie Lesec Julien Serrier Célia Seillier Benoit Bernay Caroline Regnauld Jonathane Furon Jérôme Leprince Benjamin Lefranc Denis Vivien Fabian Docagne Brigitte Le Mauff Olivier Toutirais Specific and Polyfunctional T Cell Response Against <i>N</i>-Methyl-<span style="font-variant: small-caps">d</span>-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model Biomedicines autoimmune encephalitis <i>N</i>-methyl-<span style="font-variant: small-caps">d</span>-aspartate receptor T cells B cells |
| title | Specific and Polyfunctional T Cell Response Against <i>N</i>-Methyl-<span style="font-variant: small-caps">d</span>-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model |
| title_full | Specific and Polyfunctional T Cell Response Against <i>N</i>-Methyl-<span style="font-variant: small-caps">d</span>-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model |
| title_fullStr | Specific and Polyfunctional T Cell Response Against <i>N</i>-Methyl-<span style="font-variant: small-caps">d</span>-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model |
| title_full_unstemmed | Specific and Polyfunctional T Cell Response Against <i>N</i>-Methyl-<span style="font-variant: small-caps">d</span>-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model |
| title_short | Specific and Polyfunctional T Cell Response Against <i>N</i>-Methyl-<span style="font-variant: small-caps">d</span>-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model |
| title_sort | specific and polyfunctional t cell response against i n i methyl span style font variant small caps d span aspartate receptor in an autoantibody mediated encephalitis model |
| topic | autoimmune encephalitis <i>N</i>-methyl-<span style="font-variant: small-caps">d</span>-aspartate receptor T cells B cells |
| url | https://www.mdpi.com/2227-9059/12/11/2458 |
| work_keys_str_mv | AT leonielesec specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT julienserrier specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT celiaseillier specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT benoitbernay specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT carolineregnauld specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT jonathanefuron specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT jeromeleprince specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT benjaminlefranc specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT denisvivien specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT fabiandocagne specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT brigittelemauff specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel AT oliviertoutirais specificandpolyfunctionaltcellresponseagainstinimethylspanstylefontvariantsmallcapsdspanaspartatereceptorinanautoantibodymediatedencephalitismodel |