Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation
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 fa...
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| Veröffentlicht in: | Annual review of medicine 2020-01, Vol.71 (1), p.263-276 |
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| description | 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. |
| doi_str_mv | 10.1146/annurev-med-041818-011649 |
| format | Article |
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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. 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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.</description><subject>Animals</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Cell activation</subject><subject>Chemical and Drug Induced Liver Injury - immunology</subject><subject>Chemical and Drug Induced Liver Injury - metabolism</subject><subject>Chemical and Drug Induced Liver Injury - pathology</subject><subject>Cytokines</subject><subject>Disease</subject><subject>drug target</subject><subject>fibroblast</subject><subject>Fibrosis</subject><subject>Fibrosis - immunology</subject><subject>Fibrosis - metabolism</subject><subject>Fibrosis - pathology</subject><subject>Humans</subject><subject>IL-11</subject><subject>IL11</subject><subject>inflammation</subject><subject>Inflammation - immunology</subject><subject>Inflammation - metabolism</subject><subject>Inflammatory bowel diseases</subject><subject>Inflammatory Bowel Diseases - immunology</subject><subject>Inflammatory Bowel Diseases - metabolism</subject><subject>Inflammatory Bowel Diseases - pathology</subject><subject>Inflammatory diseases</subject><subject>Interleukin 11</subject><subject>Interleukin 6</subject><subject>Interleukin-11 - immunology</subject><subject>Interleukin-11 - metabolism</subject><subject>Interleukin-11 - physiology</subject><subject>Interleukin-6 - immunology</subject><subject>Intestine</subject><subject>Kidney diseases</subject><subject>Kidney Diseases - immunology</subject><subject>Kidney Diseases - metabolism</subject><subject>Kidney Diseases - pathology</subject><subject>Liver - immunology</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver diseases</subject><subject>Lung - immunology</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Lung diseases</subject><subject>Mice</subject><subject>Myofibroblasts - immunology</subject><subject>Myofibroblasts - metabolism</subject><subject>Myofibroblasts - pathology</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - metabolism</subject><subject>Non-alcoholic Fatty Liver Disease - immunology</subject><subject>Non-alcoholic Fatty Liver Disease - metabolism</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Pulmonary Fibrosis - immunology</subject><subject>Pulmonary Fibrosis - metabolism</subject><subject>Pulmonary Fibrosis - pathology</subject><subject>Recombinant Proteins</subject><subject>Rheumatoid arthritis</subject><subject>Scleroderma, Systemic - immunology</subject><subject>Scleroderma, Systemic - metabolism</subject><subject>Scleroderma, Systemic - pathology</subject><subject>Skin - immunology</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>stroma</subject><subject>Systemic sclerosis</subject><issn>0066-4219</issn><issn>1545-326X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkFFL3jAUhsOYzE-3vzAydms0p03TZBcDEZ2CokwF78Jpm3ZxbapJq4h_fvns5w8YHHLgnPe8L3kI-QZ8H0DIA_R-DvaJDbZhXIACxTiAFPoDWUEhCpZn8u4jWXEuJRMZ6G2yE-M951znufpEtnPQSnJVrMjrqWuc76jz9KrH9F677s_0g575yYbezn-dZwD0eLChs5FiKnqBMS3pb9vNPU5joGNLT1wVxujiHr1xMc72zaALbnrZo-gbej2FccA-jdsehwEnN_rPZKvFPtovm75Lbk-Ob45O2fnlr7Ojw3OGooCJYdFqtE0JstBCaqxA8DrPs7pqoFJaZ6UsQbQ2Q50JgKyomra2Jdqay9pWMt8l3xffhzA-zjZO5n6cg0-RJsuVUqUoJCSVXlR1-kgMtjUPwQ0YXgxws8ZuNthNwm4W7GbBnm6_bhLmar19v3znnAQ_F8HaA_vk4uxz_I-Ef1Zdl1E</recordid><startdate>20200127</startdate><enddate>20200127</enddate><creator>Cook, Stuart A</creator><creator>Schafer, Sebastian</creator><general>Annual Reviews</general><general>Annual Reviews, Inc</general><scope>ZYWBE</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20200127</creationdate><title>Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation</title><author>Cook, Stuart A ; Schafer, Sebastian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a451t-a5f9aed71659469ab140c332cbd1b899276714fe2a9241125bdfce7aec06ceb63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Arthritis, Rheumatoid - pathology</topic><topic>Cell activation</topic><topic>Chemical and Drug Induced Liver Injury - immunology</topic><topic>Chemical and Drug Induced Liver Injury - metabolism</topic><topic>Chemical and Drug Induced Liver Injury - pathology</topic><topic>Cytokines</topic><topic>Disease</topic><topic>drug target</topic><topic>fibroblast</topic><topic>Fibrosis</topic><topic>Fibrosis - immunology</topic><topic>Fibrosis - metabolism</topic><topic>Fibrosis - pathology</topic><topic>Humans</topic><topic>IL-11</topic><topic>IL11</topic><topic>inflammation</topic><topic>Inflammation - immunology</topic><topic>Inflammation - metabolism</topic><topic>Inflammatory bowel diseases</topic><topic>Inflammatory Bowel Diseases - immunology</topic><topic>Inflammatory Bowel Diseases - metabolism</topic><topic>Inflammatory Bowel Diseases - pathology</topic><topic>Inflammatory diseases</topic><topic>Interleukin 11</topic><topic>Interleukin 6</topic><topic>Interleukin-11 - immunology</topic><topic>Interleukin-11 - metabolism</topic><topic>Interleukin-11 - physiology</topic><topic>Interleukin-6 - immunology</topic><topic>Intestine</topic><topic>Kidney diseases</topic><topic>Kidney Diseases - immunology</topic><topic>Kidney Diseases - metabolism</topic><topic>Kidney Diseases - pathology</topic><topic>Liver - immunology</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver diseases</topic><topic>Lung - immunology</topic><topic>Lung - metabolism</topic><topic>Lung - pathology</topic><topic>Lung diseases</topic><topic>Mice</topic><topic>Myofibroblasts - immunology</topic><topic>Myofibroblasts - metabolism</topic><topic>Myofibroblasts - pathology</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - metabolism</topic><topic>Non-alcoholic Fatty Liver Disease - immunology</topic><topic>Non-alcoholic Fatty Liver Disease - metabolism</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Pulmonary Fibrosis - immunology</topic><topic>Pulmonary Fibrosis - metabolism</topic><topic>Pulmonary Fibrosis - pathology</topic><topic>Recombinant Proteins</topic><topic>Rheumatoid arthritis</topic><topic>Scleroderma, Systemic - immunology</topic><topic>Scleroderma, Systemic - metabolism</topic><topic>Scleroderma, Systemic - pathology</topic><topic>Skin - immunology</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>stroma</topic><topic>Systemic sclerosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cook, Stuart A</creatorcontrib><creatorcontrib>Schafer, Sebastian</creatorcontrib><collection>Annual Reviews Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Annual review of medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cook, Stuart A</au><au>Schafer, Sebastian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation</atitle><jtitle>Annual review of medicine</jtitle><addtitle>Annu Rev Med</addtitle><date>2020-01-27</date><risdate>2020</risdate><volume>71</volume><issue>1</issue><spage>263</spage><epage>276</epage><pages>263-276</pages><issn>0066-4219</issn><eissn>1545-326X</eissn><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.</abstract><cop>United States</cop><pub>Annual Reviews</pub><pmid>31986085</pmid><doi>10.1146/annurev-med-041818-011649</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | Hiding in Plain Sight: Interleukin-11 Emerges as a Master Regulator of Fibrosis, Tissue Integrity, and Stromal Inflammation |
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