ArticleThe Journal of clinical investigation2021
IL-23 reshapes kidney resident cell metabolism and promotes local kidney inflammation.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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29 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Association of psoriasis with chronic kidney disease and end-stage renal disease: a systematic review and meta-analysis.Frontiers in medicine · 2023Pooled it
- Targeting a Novel AREGCell proliferation · 2026Article
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- Plasma Proteomic Profile of Dietary Potassium and Incident CKD.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Multi-cellular network model predicts alterations in glomerular endothelial structure in diabetic kidney disease.PLoS computational biology · 2025Article
- Role of Fibroblast-Immune Crosstalk in Kidney, Lung, and Skin Tertiary Lymphoid Structures.Immunological reviews · 2025Review
- Kidney immunology from pathophysiology to clinical translation.Nature reviews. Immunology · 2025Review
- The integrated stress response pathway controls cytokine production in tissue-resident memory CD4Nature immunology · 2025Article
- IL-23R is a senescence-linked circulating and tissue biomarker of aging.Nature aging · 2025Article
- Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis.Nature communications · 2024Article
- Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2024Review
- The immunoregulatory roles of non-haematopoietic cells in the kidney.Nature reviews. Nephrology · 2024Review
- Activation of BZW1 by CEBPB in macrophages promotes eIF2α phosphorylation-mediated metabolic reprogramming and endoplasmic reticulum stress in MRL/lpr lupus-prone mice.Cellular & molecular biology letters · 2023Article
- Pathogenic cellular and molecular mediators in lupus nephritis.Nature reviews. Nephrology · 2023Review
- Decipher the Immunopathological Mechanisms and Set Up Potential Therapeutic Strategies for Patients with Lupus Nephritis.International journal of molecular sciences · 2023Review
- Glucocorticoids target the CXCL9/CXCL10-CXCR3 axis and confer protection against immune-mediated kidney injury.JCI insight · 2023Article
- Targeting immunometabolism during cardiorenal injury: roles of conventional and alternative macrophage metabolic fuels.Frontiers in physiology · 2023Review
- Tertiary lymphoid structures in autoimmune diseases.Frontiers in immunology · 2023Review
- A Case Report of Adalimumab Successfully Treated a Severe Plaque Psoriasis Patient with Psoriatic End-Stage Renal Disease.Clinical, cosmetic and investigational dermatology · 2023Article
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9 authors at 4 institutions in 2 countries.
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Abstract
Interstitial kidney inflammation is present in various nephritides in which serum interleukin 23 (IL-23) is elevated. Here we showed that murine and human renal tubular epithelial cells (TECs) expressing the IL-23 receptor (IL-23R) responded to IL-23 by inducing intracellular calcium flux, enhancing glycolysis, and upregulating calcium/calmodulin kinase IV (CaMK4), which resulted in suppression of the expression of the arginine-degrading enzyme arginase 1 (ARG1), thus increasing in situ levels of free L-arginine. Limited availability of arginine suppressed the ability of infiltrating T cells to proliferate and produce inflammatory cytokines. TECs from humans and mice with nephritis expressed increased levels of IL-23R and CaMK4 but reduced levels of ARG1. TEC-specific deletion of Il23r or Camk4 suppressed inflammation, whereas deletion of Arg1 exacerbated inflammation in different murine disease models. Finally, TEC-specific delivery of a CaMK4 inhibitor specifically curbed renal inflammation in lupus-prone mice without affecting systemic inflammation. Our data offer the first evidence to our knowledge of the immunosuppressive capacity of TECs through a mechanism that involves competitive uptake of arginine and signify the importance of modulation of an inflammatory cytokine in the function of nonlymphoid cells, which leads to the establishment of an inflammatory microenvironment. New approaches to treat kidney inflammation should consider restoring the immunosuppressive capacity of TECs.
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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.