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

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...

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Bibliographic Details
Main Authors:	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
Format:	Article
Language:	English
Published:	MDPI AG 2024-10-01
Series:	Biomedicines
Subjects:	autoimmune encephalitis <i>N</i>-methyl-<span style="font-variant: small-caps">d</span>-aspartate receptor T cells B cells
Online Access:	https://www.mdpi.com/2227-9059/12/11/2458
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Summary:	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.
ISSN:	2227-9059