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| Item Type: | Preprint |
|---|---|
| Title: | Aquaporin-4-specific T cell responses in NMOSD revealed by mRNA-engineered dendritic cells |
| Creators: |
Pauly, Verena, Hastermann, Maria  ORCID: https://orcid.org/0000-0003-0769-0115, Paul, Friedemann ORCID: https://orcid.org/0000-0002-6378-0070, Garner, Craig Curtis, Cestari, Sara ORCID: https://orcid.org/0009-0004-8490-1785, Schmitz, Dietmar ORCID: https://orcid.org/0000-0003-2741-5241, Klotzsch, Enrico ORCID: https://orcid.org/0000-0002-7577-9042 and Strempel, Nadine ORCID: https://orcid.org/0009-0001-2207-177X
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| Abstract: | Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system characterized by loss of immune tolerance to the water channel aquaporin-4 (AQP4). Current therapies do not specifically restore AQP4 tolerance or selectively suppress antigen-specific immune responses. Reprogramming patient's own dendritic cells (DCs) with mRNA to induce tolerance represents a promising therapeutic strategy. A key prerequisite for this approach is generating mRNAs encoding disease-relevant autoantigens recognized by the patient's immune system. Here, we generated recombinant mRNAs encoding human AQP4 and evaluated T cell responses to autologous DCs transfected with AQP4 mRNA in eight NMOSD patients and ten healthy controls. Transfected DCs were co-cultured with autologous T cells and stimulated twice. The assay detected robust AQP4-specific T cell response in a patient with recent disease activity who was not receiving immunosuppressive therapy, demonstrating its ability to identify clinically relevant autoreactive T cell responses. These findings establish the feasibility of an mRNA-based antigen-specific T cell assay for studying NMOSD pathogenesis, stratifying patients by T cell involvement, and supporting development of personalized tolerance-inducing therapies. |
| Keywords: | Dendritic Cells, NMOSD, Aquaporin-4, mRNA Reprogramming |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2026.06.05.730365 |
| Date: | 9 June 2026 |
| Official Publication: | https://doi.org/10.64898/2026.06.05.730365 |
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