ArticleProceedings of the National Academy of Sciences of the United States of America2023
Enhanced pathogenicity of Th17 cells due to natalizumab treatment: Implications for MS disease rebound.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- The Art of Sequencing Disease-Modifying Therapies in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- LEAP2 as a therapeutic target in obesity and cardiometabolic disorders.Reviews in endocrine & metabolic disorders · 2026Review
- Pro-Inflammatory c-MetAnnals of neurology · 2026Article
- Annual 12-Week Dosing Gap of Natalizumab: Clinical Efficacy, Blood Biomarkers, and CSF Cell Composition.Annals of clinical and translational neurology · 2026Observational
- Th17 cell pathogenicity in autoimmune disease.Experimental & molecular medicine · 2025Review
- Metabolic reprogramming as a therapeutic target for modulating the Th17/Treg balance in autoimmune diseases: a comprehensive review.Frontiers in immunology · 2025Review
- The Involvement of Glial Cells in Blood-Brain Barrier Damage in Neuroimmune Diseases.International journal of molecular sciences · 2024Review
- Chemokine-mediated cell migration into the central nervous system in progressive multifocal leukoencephalopathy.Cell reports. Medicine · 2024Article
- Cerebral microvascular endothelial cell-derived extracellular vesicles regulate blood - brain barrier function.Fluids and barriers of the CNS · 2023Article
- Natalizumab Treatment Induces Proinflammatory CD4 T Cells Preferentially in the Integrin β7+ Compartment.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Integrin α3 promotes TScience immunology · 2023Article
- Implications of immunometabolism for smouldering MS pathology and therapy.Nature reviews. Neurology · 2023Review
- Targeting MCAM for next-generation modulation of leucocyte trafficking.Brain : a journal of neurology · 2023Article
- Single-cell profiling reveals preferential reduction of memory B cell subsets in cladribine patients that correlates with treatment response.Therapeutic advances in neurological disorders · 2023Article
- Alpha4 beta7 integrin controls Th17 cell trafficking in the spinal cord leptomeninges during experimental autoimmune encephalomyelitis.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After natalizumab (NAT) cessation, some multiple sclerosis (MS) patients experience a severe disease rebound. The rebound pathophysiology is still unclear; however, it has been linked to interleukin-17-producing T-helper (Th17) cells. We demonstrate that during NAT treatment, MCAM+CCR6+Th17 cells gradually acquire a pathogenic profile, including proinflammatory cytokine production, pathogenic transcriptional signatures, brain endothelial barrier impairment, and oligodendrocyte damage via induction of apoptotic pathways. This is accompanied by an increase in Th17 cell frequencies in the cerebrospinal fluid of NAT-treated patients. Notably, Th17 cells derived from NAT-treated patients, who later developed a disease rebound upon treatment cessation, displayed a distinct transcriptional pathogenicity profile associated with altered migratory properties. Accordingly, increased brain infiltration of patient Th17 cells was illustrated in a humanized mouse model and brain histology from a rebound patient. Therefore, peripheral blood-accumulated MCAM+CCR6+Th17 cells might be involved in rebound pathophysiology, and monitoring of changes in Th17 cell pathogenicity in patients before/during NAT treatment cessation might enable rebound risk assessment in the future.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.