Foxp3+ regulatory T cells expression in neuromyelitis optica spectrum disorders
Abstract
Background Alterations in the frequency or function of regulatory T cells (Tregs), which play a critical role in the maintenance of peripheral immune tolerance, are known to be involved in the pathogenesis of several autoimmune diseases. Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory diseases of the central nervous system (CNS), of which the etiology and mechanisms underlying its development are not completely understood. Although there is increasing evidence for the involvement of effector T cells in NMOSD, no data are available regarding the role of Tregs in its pathogenesis. Aim The aim of this study was to investigate the mRNA expression level of regulatory T cell genes in NMOSD. Methods We used gene expression array and RT-PCR analysis to study Treg cell genes in NMOSD RESULTS: A distinctive Treg gene signature in the peripheral blood of NMOSD patients is described, as well as significantly decreased FoxP3 mRNA expression in the peripheral blood mononuclear cells (PBMCs) of the patients vs that in the healthy controls (HCs) (NMOSD,1.8RQ vs HC, 6.8RQ, p = 0.01). Conclusions The present study shows downregulation at the mRNA expression level of a Treg key transcription factor FoxP3, in NMOSD. Exploration of Tregs function and interconnections in the peripheral immune system should advance our understanding of NMOSD pathogenesis.
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FOXP3+ AQP4-specific ThEx cells are not derived from an unstable thymic Treg precursor.
“indicating that they are not derived from an unstable thymic Treg precursor, as described in various AIDs 71,72 including NMOSD. 73-76”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [73]
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“There are several contradictory reports on Treg cells in NMOSD: Tregs-related genes were found significantly decreased in NMOSD patients [33].”
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“Recently, downregulation of Foxp3 mRNA expression was described in PBMC of NMOSD patients (51).”
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ResultThe Potential Immunoregulatory Roles of Vitamin D in Neuromyelitis Optica Spectrum Disorder.
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Lymphocyte Subsets Are Associated with Disease Status in Neuromyelitis Optica Spectrum Disorders
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“Furthermore, NMOSD patients exhibit downregulation of the Treg key transcription factor FoxP3 at the mRNA expression level, suggesting an impairment in peripheral T cell regulation [15].”
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“Peripheral immune profiling reveals enhanced type I interferon signaling, skewing toward Th17 responses, and impaired Treg function [122, 123], high-lighting a profoundly proinflammatory immune milieu.”
CD4+CD25+ regulatory T cell therapy in neurological autoimmune diseases
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“However, these fi ndings contradict those of Brill et al. [29].”
BackgroundResultTissue repair in the central nervous system: the epigenetic programming of regulatory T cells
Chenine, S., Tiane, A., Baeten, P., Verreycken, J., Knippenberg, S., Gerlach, O., Broux, B., la van den Hove, D., & Vanmierlo, T. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1916267
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Targeting MOG to skin macrophages prevents EAE in macaques through TGFβ-induced peripheral tolerancePreprint
Fovet, C.-M., Stimmer, L., Contreras, V., Horellou, P., Hubert, A., Sediki, N., Chapon, C., Tricot, S., Leroy, C., Flament, J., et al. (2019) · bioRxiv · doi:10.1101/571828
“In fact, studies in adults and children with MS or NMO have reported deficient Treg function (Brill et al, 2019) and abnormally increased Th1 and Th17 effector cells responses in the periphery (Kaneko et al, 2018; Sagan et al, 2016), which suggests that pathogenicity due to auto-reactive T cells…”
Background
- Authors
- Brill, L., Lavon, I., & Vaknin-Dembinsky, A.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Venue
- Multiple Sclerosis and Related Disorders
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 30
- Pages
- 114-118
- ISSN
- 2211-0348 (ISSN-L)
- OpenAlex
- W2913061624
- Cited by
- 28
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 7 · 2020: 1 · 2019: 4
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-05-01)
- Open access
- closed
- Locations
- Multiple Sclerosis and Related Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- neuromyelitis optica spectrum disorder, regulatory T cells, Foxp3, Foxp3 mRNA expression, peripheral blood mononuclear cells, autoimmune disease pathogenesis, immune tolerance, central nervous system autoimmunity
- MeSH terms
- Adult, Disability Evaluation, Female, Humans, Male, Middle Aged, Neuromyelitis Optica, RNA, Messenger, Cohort Studies, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Transcriptome
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