ArticleJournal of immunology (Baltimore, Md. : 1950)2012
IL-21 promotes lupus-like disease in chronic graft-versus-host disease through both CD4 T cell- and B cell-intrinsic mechanisms.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Aberrant STAT3 activation and overproduction of IL-21 in systemic lupus erythematosus: role of miR-155 and miR-21 in target genesFrontiers in immunology · 2026Article
- WDFY1-expressing follicular dendritic cells play a critical role in lupus development in cGVHD mouse model.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Functional Contributions of Antigen Presenting Cells in Chronic Graft-Versus-Host Disease.Frontiers in immunology · 2021Review
- T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor.Frontiers in immunology · 2021Review
- Emerging Biological Functions of IL-17A: A New Target in Chronic Obstructive Pulmonary Disease?Frontiers in pharmacology · 2021Review
- T follicular helper cells and T follicular regulatory cells in rheumatic diseases.Nature reviews. Rheumatology · 2019Review
- Review
- C5aR1 regulates T follicular helper differentiation and chronic graft-versus-host disease bronchiolitis obliterans.JCI insight · 2018Article
- Inducible T-Cell Co-Stimulator Impacts Chronic Graft-Versus-Host Disease by Regulating Both Pathogenic and Regulatory T Cells.Frontiers in immunology · 2018Article
- Induction therapy downregulates the expression of Th17/Tfh cytokines in patients with active lupus nephritis.American journal of clinical and experimental immunology · 2018Article
- Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective.Trends in molecular medicine · 2017Review
- RGC-32 Promotes Th17 Cell Differentiation and Enhances Experimental Autoimmune Encephalomyelitis.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- RGC-32 is a novel regulator of the T-lymphocyte cell cycle.Experimental and molecular pathology · 2015Article
- Interleukin-21, a potential diagnostic and therapeutic target for systemic lupus erythematosus.Rheumatology international · 2014Article
- IL-21 promotes late activator APC-mediated T follicular helper cell differentiation in experimental pulmonary virus infection.PloS one · 2014Article
- IL-21 is a double-edged sword in the systemic lupus erythematosus-like disease of BXSB.Yaa mice.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Autoimmunity in 2012.Clinical reviews in allergy & immunology · 2013Review
- The cellular source and target of IL-21 in K/BxN autoimmune arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Decreased serum level of IL-21 in new-onset systemic lupus erythematosus patients.Rheumatology international · 2013Article
- T follicular helper cells mediate expansion of regulatory B cells via IL-21 in Lupus-prone MRL/lpr mice.PloS one · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
T cell-driven B cell hyperactivity plays an essential role in driving autoimmune disease development in systemic lupus erythematosus. IL-21 is a member of the type I cytokine family with pleiotropic activities. It regulates B cell differentiation and function, promotes T follicular helper (T(FH)) cell and Th17 cell differentiation, and downregulates the induction of T regulatory cells. Although IL-21 has been implicated in systemic lupus erythematosus, the relative importance of IL-21R signaling in CD4(+) T cells versus B cells is not clear. To address this question, we took advantage of two induced models of lupus-like chronic graft-versus-host disease by using wild-type or IL-21R(-/-) mice as donors in the parent-into-F1 model and as hosts in the Bm12→B6 model. We show that IL-21R expression on donor CD4(+) T cells is essential for sustaining T(FH) cell number and subsequent help for B cells, resulting in autoantibody production and more severe lupus-like renal disease, but it does not alter the balance of Th17 cells and regulatory T cells. In contrast, IL-21R signaling on B cells is critical for the induction and maintenance of germinal centers, plasma cell differentiation, autoantibody production, and the development of renal disease. These results demonstrate that IL-21 promotes autoimmunity in chronic graft-versus-host disease through both CD4(+) T cell- and B cell-intrinsic mechanisms and suggest that IL-21 blockade may attenuate B cell hyperactivity, as well as the aberrant T(FH) cell pathway that contributes to lupus pathogenesis.
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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.