ArticleThe Journal of clinical investigation2015
IL-21R signaling is critical for induction of spontaneous experimental autoimmune encephalomyelitis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Monoclonal Antibodies in Preclinical EAE Models of Multiple Sclerosis: A Systematic Review.International journal of molecular sciences · 2017Pooled it
- Role of Antibody Glycosylation in Health, Disease, and Therapy.Handbook of experimental pharmacology · 2025Review
- Myelin-reactive B cells exacerbate CD4Nature communications · 2024Article
- The identification and expression of an interleukin-21 receptor in large yellow croaker (Larimichthys crocea).Molecular biology reports · 2023Article
- Article
- Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis.Cell death and differentiation · 2023Article
- Tertiary lymphoid structures in autoimmune diseases.Frontiers in immunology · 2023Review
- Article
- Therapeutic Effect of IL-21 Blockage by Gene Therapy in Experimental Autoimmune Encephalomyelitis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- IL-21/IL-21R Regulates the Neutrophil-Mediated Pathologic Immune Response during Chlamydial Respiratory Infection.Mediators of inflammation · 2022Article
- Ectopic lymphoid follicles in progressive multiple sclerosis: From patients to animal models.Immunology · 2021Review
- Cytokines that Modulate the Differentiation of Th17 Cells in Autoimmune Uveitis.Journal of immunology research · 2021Review
- Sweet Rules: Linking Glycosylation to Antibody Function.Experientia supplementum (2012) · 2021Review
- The Heat Shock Protein HSP70 Promotes Th17 Genes' Expression via Specific Regulation of microRNA.International journal of molecular sciences · 2020Article
- SKI and SMAD4 are essential for IL-21-induced Th17 differentiation.Molecular immunology · 2019Article
- IL-11 antagonist suppresses Th17 cell-mediated neuroinflammation and demyelination in a mouse model of relapsing-remitting multiple sclerosis.Clinical immunology (Orlando, Fla.) · 2018Article
- Emerging Role of Follicular T Helper Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.International journal of molecular sciences · 2018Review
- The Interleukin (IL)-23/T helper (Th)17 Axis in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis.Cold Spring Harbor perspectives in medicine · 2018Review
- Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns.PloS one · 2018Article
- IL-21 and T Cell Differentiation: Consider the Context.Trends in immunology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
IL-17-producing CD4+ T cells (Th17 cells) have well-described pathogenic roles in tissue inflammation and autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE); however, the involvement of IL-21 in these processes has remained controversial. While IL-21 is an essential autocrine amplification factor for differentiation of Th17 cells, the loss of IL-21 or IL-21 receptor (IL-21R) does not protect mice from actively induced EAE. Here, we utilized a transgenic EAE mouse model, in which T and B cells overexpress receptors for myelin oligodendrocyte glycoprotein (MOG) (referred to as 2D2xTH mice), and demonstrated that IL-21 is critical for the development of a variant form of spontaneous EAE in these animals. Il21r deletion in 2D2xTH mice reduced the incidence and severity of spontaneous EAE, which was associated with a defect in Th17 cell generation. Moreover, IL-21R deficiency limited IL-23R expression on Th17 cells and inhibited expression of key molecules involved in the generation of pathogenic Th17 cells. Conversely, loss of IL-23R in 2D2xTH mice resulted in complete resistance to the development of spontaneous EAE. Our data identify a previously unappreciated role for IL-21 in EAE and reveal that IL-21-mediated signaling supports generation and stabilization of pathogenic Th17 cells and development of spontaneous autoimmunity.
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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.