Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation

• Published in: Annual review of medicine 2020-01, Vol.71 (1), p.263-276
• Main Authors: Cook, Stuart A, Schafer, Sebastian
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Cell activation; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Cytokines; Disease; drug target; fibroblast; Fibrosis; Fibrosis - immunology; Fibrosis - metabolism; Fibrosis - pathology; Humans; IL-11; IL11; inflammation; Inflammation - immunology; Inflammation - metabolism; Inflammatory bowel diseases; Inflammatory Bowel Diseases - immunology; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - pathology; Inflammatory diseases; Interleukin 11; Interleukin 6; Interleukin-11 - immunology; Interleukin-11 - metabolism; Interleukin-11 - physiology; Interleukin-6 - immunology; Intestine; Kidney diseases; Kidney Diseases - immunology; Kidney Diseases - metabolism; Kidney Diseases - pathology; Liver - immunology; Liver - metabolism; Liver - pathology; Liver diseases; Lung - immunology; Lung - metabolism; Lung - pathology; Lung diseases; Mice; Myofibroblasts - immunology; Myofibroblasts - metabolism; Myofibroblasts - pathology; Neoplasms - immunology; Neoplasms - metabolism; Non-alcoholic Fatty Liver Disease - immunology; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - pathology; Pulmonary Fibrosis - immunology; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Recombinant Proteins; Rheumatoid arthritis; Scleroderma, Systemic - immunology; Scleroderma, Systemic - metabolism; Scleroderma, Systemic - pathology; Skin - immunology; Skin - metabolism; Skin - pathology; stroma; Systemic sclerosis
• ISSN: 0066-4219; 1545-326X
• DOI: 10.1146/annurev-med-041818-011649

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.