ArticleCellular & molecular immunology2023
The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARγ.
Article in Cellular & molecular immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 15 citations in OpenAlex.
- Targeted activation of PPARG or AKT1 alleviates liver injury in mice with type 2 diabetes and sepsis by modulating inflammatory and metabolic pathways.Annals of medicine · 2026Article
- Cytokine multimerization: when more is more and sometimes less.Nature reviews. Immunology · 2026Review
- PPARγ contributes to cardioprotection against heat stroke through ABCC5-dependent lipid metabolism.Redox biology · 2026Article
- PPAR-γ suppresses macrophage senescence and allergic airway inflammation through controlling lipid metabolic pathways.EBioMedicine · 2026Article
- The complex role of IL-37 in cancer pathogenesis: exploring its influence on hallmarks of cancer.Frontiers in immunology · 2026Review
- The regulatory role of IL-37 and IL-38 in CAR-T associated cytokine release syndrome in multiple myeloma.Frontiers in immunology · 2026Review
- The diagnostic and immunomodulatory role of IL-37 in pediatric sepsis.Frontiers in immunology · 2026Article
- Combined Analysis of Transcriptome and Mendelian Randomization RevealsJournal of inflammation research · 2025Article
- IL-37 Isoform A Prevents Collagen-Induced Arthritis in Mice by Modulating the Th17/Treg Balance via IL1R8 Receptors.International journal of molecular sciences · 2024Article
- PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap.Respiratory research · 2024Article
- PPARγ Attenuates Cellular Senescence of Alveolar Macrophages in Asthma- COPD Overlap.Research square · 2024Article
- Thirteen years to get from b to a: one of the neglected isoforms of IL-37 enters the stage.Cellular & molecular immunology · 2024Article
- Endotoxin tolerance and trained immunity: breaking down immunological memory barriers.Frontiers in immunology · 2024Review
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22 authors at 10 institutions in 6 countries.
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Abstract
Cytokine storms are crucial in the development of various inflammatory diseases, including sepsis and autoimmune disorders. The immunosuppressive cytokine INTERLEUKIN (IL)-37 consists of five isoforms (IL-37a-e). We identified IL-37a as a nuclear cytokine for the first time. Compared to IL-37b, IL-37a demonstrated greater efficacy in protecting against Toll-like receptor-induced cytokine hypersecretion and lethal endotoxic shock. The full-length (FL) form of IL-37a and the N-terminal fragment, which is processed by elastase, could translocate into cell nuclei through a distinctive nuclear localization sequence (NLS)/importin nuclear transport pathway. These forms exerted their regulatory effects independent of the IL-1R8 receptor by transcriptionally upregulating the nuclear receptor peroxisome proliferator-activated receptor (PPARγ). This process involved the recruitment of the H3K4 methyltransferase complex WDR5/MLL4/C/EBPβ and H3K4me1/2 to the enhancer/promoter of Pparg. The receptor-independent regulatory pathway of the nuclear IL-37a-PPARγ axis and receptor-dependent signaling by secreted IL-37a maintain homeostasis and are potential therapeutic targets for various inflammatory diseases, including sepsis.
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