ArticleInternational journal of molecular sciences2021
Interleukin-17 and Th17 Lymphocytes Directly Impair Motoneuron Survival of Wildtype and FUS-ALS Mutant Human iPSCs.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Assessing causal relationship between circulating cytokines and age-related neurodegenerative diseases: a bidirectional two-sample Mendelian randomization analysis.Scientific reports · 2023Pooled it
- Immune imbalance between T helper 1, T helper 17 and regulatory T cells fuels amyotrophic lateral sclerosis pathogenesis: disease trajectory, diagnosis and therapeutic implications.Journal of neuroinflammation · 2026Review
- A myeloid trisomy 21-associated gene variant is protective from Alzheimer's disease.Nature neuroscience · 2026Article
- Spatiotemporal Dynamics and Cellular States of Neuroinflammation in Amyotrophic Lateral Sclerosis: Implications for Stage‑Specific Therapeutics.ASN neuro · 2026Review
- Immune checkpoint changes correlate with the progression and prognosis of amyotrophic lateral sclerosis.Annals of medicine · 2025Article
- Novel insights into the ROCK-JAK-STAT signaling pathway in upper respiratory tract infections and neurodegenerative diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Targeting gut-brain-immune axis in amyotrophic lateral sclerosis.Frontiers in immunology · 2025Review
- The Current Landscape of Hypotheses Describing the Contribution of CD4+ Heterogeneous Populations to ALS.Current issues in molecular biology · 2024Article
- Article
- A Trisomy 21-linked Hematopoietic Gene Variant in Microglia Confers Resilience in Human iPSC Models of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- Myeloid and lymphoid expression ofScience translational medicine · 2024Article
- Insights on the Multifaceted Roles of Wild-Type and Mutated Superoxide Dismutase 1 in Amyotrophic Lateral Sclerosis Pathogenesis.Antioxidants (Basel, Switzerland) · 2023Review
- Immunology of amyotrophic lateral sclerosis - role of the innate and adaptive immunity.Frontiers in neuroscience · 2023Review
- Advances on Cellular Clonotypic Immunity in Amyotrophic Lateral Sclerosis.Brain sciences · 2022Review
- The role of Th17 cells/IL-17A in AD, PD, ALS and the strategic therapy targeting on IL-17A.Journal of neuroinflammation · 2022Review
- Progranulin Suppressed Autoimmune Uveitis and Autoimmune Neuroinflammation by Inhibiting Th1/Th17 Cells and Promoting Treg Cells and M2 Macrophages.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Th17 cells and inflammation in neurological disorders: Possible mechanisms of action.Frontiers in immunology · 2022Review
- Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis.Frontiers in aging neuroscience · 2022Review
- Neuroinflammation in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia and the Interest of Induced Pluripotent Stem Cells to Study Immune Cells Interactions With Neurons.Frontiers in molecular neuroscience · 2021Review
- Unleashing nature's potential and limitations: Exploring molecular targeted pathways and safe alternatives for the treatment of multiple sclerosis (Review).Medicine internationalReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive disease leading to the degeneration of motor neurons (MNs). Neuroinflammation is involved in the pathogenesis of ALS; however, interactions of specific immune cell types and MNs are not well studied. We recently found a shift toward T helper (Th)1/Th17 cell-mediated, pro-inflammatory immune responses in the peripheral immune system of ALS patients, which positively correlated with disease severity and progression. Whether Th17 cells or their central mediator, Interleukin-17 (IL-17), directly affects human motor neuron survival is currently unknown. Here, we evaluated the contribution of Th17 cells and IL-17 on MN degeneration using the co-culture of iPSC-derived MNs of fused in sarcoma (FUS)-ALS patients and isogenic controls with Th17 lymphocytes derived from ALS patients, healthy controls, and multiple sclerosis (MS) patients (positive control). Only Th17 cells from MS patients induced severe MN degeneration in FUS-ALS as well as in wildtype MNs. Their main effector, IL-17A, yielded in a dose-dependent decline of the viability and neurite length of MNs. Surprisingly, IL-17F did not influence MNs. Importantly, neutralizing IL-17A and anti-IL-17 receptor A treatment reverted all effects of IL-17A. Our results offer compelling evidence that Th17 cells and IL-17A do directly contribute to MN degeneration.
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Registered trials
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.