ArticleJournal of neuroinflammation2020
Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Selected Cytokines and Matrix Metalloproteinases in Pathogenesis and Treatment of Multiple Sclerosis.International journal of molecular sciences · 2026Review
- IL-9R/Arg1 pathway promotes polyamine metabolism in human airway macrophages.The Journal of allergy and clinical immunology · 2026Article
- Remote Ischemic Postconditioning Attenuates Neuroinflammation and Suggests a Potential Benefit for Early Neurological Recovery after Subarachnoid Hemorrhage via the IL-9/JAK2-STAT5 Signaling Pathway.Translational stroke research · 2026Article
- Alzheimer's disease risk protein SorLA regulates ER homeostasis and lipid metabolism in human microglia, with conserved effects in neurons.Acta neuropathologica · 2026Article
- Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Interleukin-9 Regulates NF-kB-Mediated Activation of Astrocytes in Multiple Sclerosis Brain.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Reprogramming brain-resident macrophages: from disease drivers to therapeutic allies in neurological disorders.Frontiers in cellular neuroscience · 2026Review
- The role of the IL-9‒NLRP3 axis in insulin resistance and adipose tissue inflammation during diet-induced obesity.Cellular & molecular immunology · 2025Article
- Modulation of retinal inflammation delays degeneration in a mouse model of geographic atrophy.Scientific reports · 2025Article
- Article
- Neuroinflammation and Amyotrophic Lateral Sclerosis: Recent Advances in Anti-Inflammatory Cytokines as Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Emerging Insights into the Role of Macrophages in Multiple Sclerosis: Pathogenesis and Potential Therapeutic Strategies.Journal of inflammation research · 2025Review
- Article
- Differentiation and regulation of CD4Cellular and molecular life sciences : CMLS · 2024Review
- Review
- Cytokine Profiling in Cerebrospinal Fluid of Patients with Newly Diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS): Associations between Inflammatory Biomarkers and Disease Activity.International journal of molecular sciences · 2024Article
- Locus of (IL-9) control: IL9 epigenetic regulation in cellular function and human disease.Experimental & molecular medicine · 2024Review
- Exposure to structurally unique β-d-glucans differentially affects inflammatory responses in male mouse lungs.Physiological reports · 2024Article
- Interleukin-9 protects from microglia- and TNF-mediated synaptotoxicity in experimental multiple sclerosis.Journal of neuroinflammation · 2024Article
- Interleukins in Epilepsy: Friend or Foe.Neuroscience bulletin · 2024Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundMultiple sclerosis (MS) is an immune-mediated, chronic inflammatory, and demyelinating disease of the central nervous system (CNS). Several cytokines are thought to be involved in the regulation of MS pathogenesis. We recently identified interleukin (IL)-9 as a cytokine reducing inflammation and protecting from neurodegeneration in relapsing-remitting MS patients. However, the expression of IL-9 in CNS, and the mechanisms underlying the effect of IL-9 on CNS infiltrating immune cells have never been investigated.
methodsTo address this question, we first analyzed the expression levels of IL-9 in post-mortem cerebrospinal fluid of MS patients and the in situ expression of IL-9 in post-mortem MS brain samples by immunohistochemistry. A complementary investigation focused on identifying which immune cells express IL-9 receptor (IL-9R) by flow cytometry, western blot, and immunohistochemistry. Finally, we explored the effect of IL-9 on IL-9-responsive cells, analyzing the induced signaling pathways and functional properties.
resultsWe found that macrophages, microglia, and CD4 T lymphocytes were the cells expressing the highest levels of IL-9 in the MS brain. Of the immune cells circulating in the blood, monocytes/macrophages were the most responsive to IL-9. We validated the expression of IL-9R by macrophages/microglia in post-mortem brain sections of MS patients. IL-9 induced activation of signal transducer and activator of transcription (STAT)1, STAT3, and STAT5 and reduced the expression of activation markers, such as CD45, CD14, CD68, and CD11b in inflammatory macrophages stimulated in vitro with lipopolysaccharide and interferon (IFN)-γ. Similarly, in situ the number of activated CD68
conclusionsThese results reveal a new cytokine expressed in the CNS, with a role in the context of MS. We have demonstrated that IL-9 and its receptor are both expressed in CNS. Moreover, we found that IL-9 decreases the activation state and promotes the anti-inflammatory properties of human macrophages. This mechanism may contribute to the beneficial effects of IL-9 that are observed in MS, and may be therapeutically potentiated by modulating IL-9 expression in MS.
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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.