Bibliographic Details
| Title: |
Neuron-reactive KIR + CD8 + T cells display an encephalitogenic transcriptional program in autoimmune encephalitis |
| Authors: |
Perriot, Sylvain, Jones, Samuel, Genolet, Raphaël, Mathias, Amandine, Lindsay, Helen, Bobisse, Sara, Di Liberto, Giovanni, Canales, Mathieu, Queiroz, Lise, Sauvage, Christophe, Wagner, Ingrid, Oberholster, Larise, Gimenez, Marie, Bégarie, Diane, Kovac, Stjepana, Desestret, Virginie, Théaudin, Marie, Pot, Caroline, Wiendl, Heinz, Honnorat, Jérôme, Merkler, Doron, Gottardo, Raphaël, Harari, Alexandre Max-Albert, Du Pasquier, Renaud Alfred Robert |
| Source: |
ISSN: 2041-1723 ; Nature communications, vol. 16, no. 1 (2025) 8568. |
| Publication Year: |
2025 |
| Collection: |
Université de Genève: Archive ouverte UNIGE |
| Subject Terms: |
info:eu-repo/classification/ddc/616.07, Humans, CD8-Positive T-Lymphocytes / immunology, CD8-Positive T-Lymphocytes / metabolism, Neurons / immunology, Neurons / metabolism, Encephalitis / immunology, Encephalitis / genetics, Encephalitis / pathology, Receptors, KIR / metabolism, KIR / immunology, KIR / genetics, Hashimoto Disease / immunology, Hashimoto Disease / genetics, Hashimoto Disease / pathology, Female, Male, Ikaros Transcription Factor / genetics, Ikaros Transcription Factor / metabolism, Middle Aged, Induced Pluripotent Stem Cells / immunology, Adult, Single-Cell Analysis, Interferon-gamma / genetics, Interferon-gamma / metabolism, Aged, Transcription, Genetic |
| Description: |
Autoreactive CD8 + T cells targeting neurons are the principal suspects in autoimmune encephalitis (AIE), but supporting data is still lacking. Here we identify neuron-reactive CD8 + T cells in a cohort of six healthy donors and one patient with anti-Ri encephalitis (Ri-AIE) by querying natural antigen presentation of neurons that are derived from human induced pluripotent stem cells. Single-cell RNA sequencing of ex vivo CD8 + T cells in an extended cohort of seven Ri-AIE patients and three aged-matched controls further reveal that these neuron-reactive CD8 + T cells correspond to cytotoxic KIR + CD8 + regulatory T cells. Intriguingly, KIR + CD8 + T cells from most Ri-AIE patients have reduced expression of KIR and the key regulatory transcription factor, Helios, encoded by the IKZF2 gene; by contrast, these cells show activated TCR signaling and increased TNF and IFNG gene expression. Importantly, Ri-AIE-derived KIR + CD8 + T cells from blood also express higher levels of TOX, a gene associated with encephalitogenic potential, and is expressed in cytotoxic CD8 + T cells in the brain lesions of one Ri-AIE patient. Altogether, our data hints that dysregulated activity of neuron-reactive cytotoxic KIR + CD8 + T cells may contribute to Ri-AIE pathogenesis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41022795; info:eu-repo/grantAgreement/EC/H2020/865026/EU/Molecular pathology of anti-viral T cell responses in the central nervous system/PATHOCODE; unige:190071 |
| Availability: |
https://archive-ouverte.unige.ch/unige:190071 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.FF76E1B9 |
| Database: |
BASE |