ArticleRheumatology (Oxford, England)2021
IL11 is elevated in systemic sclerosis and IL11-dependent ERK signalling underlies TGFβ-mediated activation of dermal fibroblasts.
Article in Rheumatology (Oxford, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- Interleukin-11 Signaling in Liver Disease: Mechanisms, Cellular Crosstalk, and Therapeutic Potential.Biomolecules · 2026Review
- Long Noncoding RNA H19 Mediates STAT3-Dependent Activation of Keratinocytes and Fibroblasts in Systemic Sclerosis Skin.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- MEOX1 Coordinates Autocrine-Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IL-11 receptor is a novel target for drug development with pharmacological activity in fibro-inflammatory disease.Scientific reports · 2026Review
- Article
- IL-11 acts as an alarmin-like pro-inflammatory mediator regulating mucosal responses during helminth infection.Mucosal immunology · 2026Article
- Article
- The role of IL-11 in chronic diseases.Frontiers in immunology · 2026Review
- Article
- Systemic sclerosis, main culprits and involved signaling pathways.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Pathogenesis of systemic sclerosis: an integrative review of recent advances.Journal of rheumatic diseases · 2025Review
- Promoting ER stress in a plasmacytoid dendritic cell line drives fibroblast activation.Cell communication and signaling : CCS · 2025Article
- Aberrant Chitinase 3-Like 1 Expression in Basal Cells Contributes to Systemic Sclerosis Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Emerging roles for interleukin-11 in the inflammatory response of intracerebral hemorrhage.Frontiers in neurology · 2025Review
- Fibroblast-derived interleukin-11 as a potential biomarker for intestinal fibrostenosis in Crohn's disease.Therapeutic advances in gastroenterology · 2025Article
- Targeting CD13/Aminopeptidase N as a Novel Therapeutic Approach for Scleroderma Fibrosis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- An Update on Molecular Mechanisms of Scarring-A Narrative Review.International journal of molecular sciences · 2024Review
- Inhibiting IL11: a novel approach to turning back the clock.Immunity & ageing : I & A · 2024Article
- Commensal microbiome dysbiosis elicits interleukin-8 signaling to drive fibrotic skin disease.PNAS nexus · 2024Article
- The Influence of IL-11 on Cardiac Fibrosis in Experimental Models: A Systematic Review.Journal of cardiovascular development and disease · 2024Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
objectivesInterleukin 11 (IL11) is highly upregulated in skin and lung fibroblasts from patients with systemic sclerosis (SSc). Here we tested whether IL11 is mechanistically linked with activation of human dermal fibroblasts (HDFs) from patients with SSc or controls.
methodsWe measured serum IL11 levels in volunteers and patients with early diffuse SSc and manipulated IL11 signalling in HDFs using gain- and loss-of-function approaches that we combined with molecular and cellular phenotyping.
resultsIn patients with SSc, serum IL11 levels are elevated as compared with healthy controls. All transforming growth factor beta (TGFβ) isoforms induced IL11 secretion from HDFs, which highly express IL11 receptor α-subunit and the glycoprotein 130 (gp130) co-receptor, suggestive of an autocrine loop of IL11 activity in HDFs. IL11 stimulated ERK activation in HDFs and resulted in HDF-to-myofibroblast transformation and extracellular matrix secretion. The pro-fibrotic action of IL11 in HDFs appeared unrelated to STAT3 activity, independent of TGFβ upregulation and was not associated with phosphorylation of SMAD2/3. Inhibition of IL11 signalling using either a neutralizing antibody against IL11 or siRNA against IL11RA reduced TGFβ-induced HDF proliferation, matrix production and cell migration, which was phenocopied by pharmacological inhibition of ERK.
conclusionsThese data reveal that autocrine IL11-dependent ERK activity alone or downstream of TGFβ stimulation promotes fibrosis phenotypes in dermal fibroblasts and suggest IL11 as a potential therapeutic target in SSc.
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