ArticleInternational journal of molecular sciences2023
T Follicular Helper Cells in Tertiary Lymphoid Structure Contribute to Renal Fibrosis by IL-21.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- T-Cell Remodeling in Renal Fibrosis: From Acute Injury to Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Tertiary Lymphoid Structure: A Potential Therapeutic Target Affecting Immune Response in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2026Review
- Pathogenesis of renal involvement in primary Sjögren's disease: convergence of multifactorial mechanisms on immune dysregulation.Frontiers in immunology · 2026Review
- Immune dysregulation inFrontiers in immunology · 2026Review
- Proteomic insights into aprotinin's immunomodulatory effects in attenuating renal fibrosis in a unilateral ureteral obstruction model.Frontiers in immunology · 2026Article
- Histological grading of tertiary lymphoid structures correlates with renal impairment and adverse outcomes in ANCA-associated glomerulonephritis.Frontiers in immunology · 2026Article
- Tertiary Lymphoid Structures Across Organs: Context, Composition, and Clinical Levers.Immunological reviews · 2025Review
- Tertiary Lymphoid Structures in Tuberculosis: Persistence, Protection, and Pathology.Immunological reviews · 2025Review
- Enhanced Therapeutic Effect of IL-10-ADSCs on Rabbit Autoimmune Dacryoadenitis By Suppressing T Follicular Helper Cell Responses Via miR-142-5p/RC3H1 Axis.Investigative ophthalmology & visual science · 2025Article
- From heterogeneity to prognosis: understanding the complexity of tertiary lymphoid structures in tumors.Molecular biology reports · 2025Review
- Clinical and Pathological Characteristics and Prognosis of Diabetic Nephropathy Patients With Tertiary Lymphoid Structures.Journal of diabetes research · 2025Article
- Revolutionizing Autoimmune Kidney Disease Treatment with Chimeric Antigen Receptor-T Cell Therapy.Research (Washington, D.C.) · 2025Review
- To reveal biomarkers related to macrophage and lactic acid metabolism in renal fibrosis and explore their mechanisms.Frontiers in immunology · 2025Article
- Occurrence and role of Tph cells in various renal diseases.Molecular medicine (Cambridge, Mass.) · 2024Review
- Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2024Review
- Exploring the crosstalk molecular mechanisms between IgA nephropathy and Sjögren's syndrome based on comprehensive bioinformatics and immunohistochemical analyses.Clinical and experimental medicine · 2024Article
- DNA methylation and whole-genome transcription analysis in CD4Clinical epigenetics · 2024Article
- Peripheral Blood Lymphocyte Subsets and Clinical Parameters in Patients Undergoing Renal Biopsy.Kidney diseases (Basel, Switzerland)Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Tertiary lymphoid structure (TLS) represents lymphocyte clusters in non-lymphoid organs. The formation and maintenance of TLS are dependent on follicular helper T (TFH) cells. However, the role of TFH cells during renal TLS formation and the renal fibrotic process has not been comprehensively elucidated in chronic kidney disease. Here, we detected the circulating TFH cells from 57 IgAN patients and found that the frequency of TFH cells was increased in IgA nephropathy patients with renal TLS and also increased in renal tissues from the ischemic-reperfusion-injury (IRI)-induced TLS model. The inducible T-cell co-stimulator (ICOS) is one of the surface marker molecules of TFH. Remarkably, the application of an ICOS-neutralizing antibody effectively prevented the upregulation of TFH cells and expression of its canonical functional mediator IL-21, and also reduced renal TLS formation and renal fibrosis in IRI mice in vivo. In the study of this mechanism, we found that recombinant IL-21 could directly promote renal fibrosis and the expression of p65. Furthermore, BAY 11-7085, a p65 selective inhibitor, could effectively alleviate the profibrotic effect induced by IL-21 stimulation. Our results together suggested that TFH cells contribute to TLS formation and renal fibrosis by IL-21. Targeting the ICOS-signaling pathway network could reduce TFH cell infiltration and alleviate renal fibrosis.
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