Abstract
Interleukin (IL)-11 is upregulated in a wide variety of fibro-inflammatory diseases such as systemic sclerosis, rheumatoid arthritis, pulmonary fibrosis, inflammatory bowel disease, kidney disease, drug-induced liver injury, and nonalcoholic steatohepatitis. IL-11 is a member of the IL-6 cytokine family and has several distinct properties that define its unique and nonredundant roles in disease. The IL-11 receptor is highly expressed on stromal, epithelial and polarized cells, where noncanonical IL-11 signaling drives the three pathologies common to all fibro-inflammatory diseases-myofibroblast activation, parenchymal cell dysfunction, and inflammation-while also inhibiting tissue regeneration. This cytokine has been little studied, and publications on IL-11 peaked in the early 1990s, when it was largely misunderstood. Here we describe recent advances in our understanding of IL-11 biology, outline how misconceptions as to its function came about, and highlight the large potential of therapies targeting IL-11 signaling for treating human disease.
Keywords:
IL-11; IL11; drug target; fibroblast; fibrosis; inflammation; interleukin-11; stroma.
MeSH terms
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Animals
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Arthritis, Rheumatoid / immunology
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Arthritis, Rheumatoid / metabolism
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Arthritis, Rheumatoid / pathology
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Chemical and Drug Induced Liver Injury / immunology
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Chemical and Drug Induced Liver Injury / metabolism
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Chemical and Drug Induced Liver Injury / pathology
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Fibrosis / immunology*
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Fibrosis / metabolism
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Fibrosis / pathology
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Humans
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Inflammation / immunology*
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Inflammation / metabolism
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Inflammatory Bowel Diseases / immunology
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Inflammatory Bowel Diseases / metabolism
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Inflammatory Bowel Diseases / pathology
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Interleukin-11 / immunology*
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Interleukin-11 / metabolism
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Interleukin-11 / physiology
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Interleukin-6 / immunology
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Kidney Diseases / immunology
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Kidney Diseases / metabolism
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Kidney Diseases / pathology
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Liver / immunology
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Liver / metabolism
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Liver / pathology
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Lung / immunology
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Lung / metabolism
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Lung / pathology
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Mice
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Myofibroblasts / immunology
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Myofibroblasts / metabolism
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Myofibroblasts / pathology
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Neoplasms / immunology
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Neoplasms / metabolism
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Non-alcoholic Fatty Liver Disease / immunology
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Non-alcoholic Fatty Liver Disease / metabolism
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Non-alcoholic Fatty Liver Disease / pathology
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Pulmonary Fibrosis / immunology
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Pulmonary Fibrosis / metabolism
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Pulmonary Fibrosis / pathology
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Recombinant Proteins
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Scleroderma, Systemic / immunology
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Scleroderma, Systemic / metabolism
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Scleroderma, Systemic / pathology
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Skin / immunology
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Skin / metabolism
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Skin / pathology
Substances
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Interleukin-11
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Interleukin-6
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Recombinant Proteins