Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases
Epithelial cell proliferation, division, and differentiation are critical for barrier repair following inflammation, but the initial trigger for this process is unknown. Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal...
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| Veröffentlicht in: | The Journal of experimental medicine 2019-09, Vol.216 (9), p.2184-2201 |
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| creator | Fujino, Naoya Brand, Oliver J Morgan, David J Fujimori, Toshifumi Grabiec, Aleksander M Jagger, Christopher P Maciewicz, Rose A Yamada, Mitsuhiro Itakura, Koji Sugiura, Hisatoshi Ichinose, Masakazu Hussell, Tracy |
| description | Epithelial cell proliferation, division, and differentiation are critical for barrier repair following inflammation, but the initial trigger for this process is unknown. Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal cell expansion, cell cycle reentry, and symmetrical cell division. Furthermore, once the pool of tracheal basal cells has expanded, silencing of Axl is required for their differentiation. Genetic depletion of Axl triggers asymmetrical cell division, leading to epithelial differentiation and ciliated cell regeneration. This discovery has implications for conditions associated with epithelial barrier dysfunction, basal cell hyperplasia, and continued turnover of dying cells in patients with chronic inflammatory pulmonary diseases. |
| doi_str_mv | 10.1084/jem.20171978 |
| format | Article |
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Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal cell expansion, cell cycle reentry, and symmetrical cell division. Furthermore, once the pool of tracheal basal cells has expanded, silencing of Axl is required for their differentiation. Genetic depletion of Axl triggers asymmetrical cell division, leading to epithelial differentiation and ciliated cell regeneration. 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Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal cell expansion, cell cycle reentry, and symmetrical cell division. Furthermore, once the pool of tracheal basal cells has expanded, silencing of Axl is required for their differentiation. Genetic depletion of Axl triggers asymmetrical cell division, leading to epithelial differentiation and ciliated cell regeneration. This discovery has implications for conditions associated with epithelial barrier dysfunction, basal cell hyperplasia, and continued turnover of dying cells in patients with chronic inflammatory pulmonary diseases.</description><subject>Aged</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Axl Receptor Tyrosine Kinase</subject><subject>Cell Cycle</subject><subject>Cell Proliferation</subject><subject>DNA - biosynthesis</subject><subject>Epithelium - pathology</subject><subject>Female</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Inflammation - enzymology</subject><subject>Inflammation - pathology</subject><subject>Lung - pathology</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Orthomyxoviridae - physiology</subject><subject>Orthomyxoviridae Infections - immunology</subject><subject>Orthomyxoviridae Infections - virology</subject><subject>Proto-Oncogene Proteins - deficiency</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Pulmonary Disease, Chronic Obstructive - enzymology</subject><subject>Pulmonary Disease, Chronic Obstructive - pathology</subject><subject>Re-Epithelialization</subject><subject>Receptor Protein-Tyrosine Kinases - deficiency</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Trachea - pathology</subject><subject>Trans-Activators - metabolism</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctP3DAQxi1UBFvaW8-Vjz0QGD-S2JdKCBWKhMQBOFuzsb1r5MSpnaDy3zfLS0UaaQ7zm28eHyHfGJwwUPL0wfUnHFjLdKv2yIrVEipdC_WJrAA4rxhAe0g-l_IAwKSsmwNyKBhXmrFmReytG0oYNjR5imMapzSFjnYuxkKnbU7zZkvP_kba4VxcoXFe0DUWjM8MHXOKwbuMU0gDDbvwEfsep5SfqA3F4dL2hex7jMV9fc1H5P7i19357-r65vLq_Oy66qSWU9UyJ1qtxFq0wikUUgkL1kpEDUpZ5ZGLTiNIKz3XjXUNMK_AW1jaQTXiiPx80R3nde9s54YpYzRjDj3mJ5MwmI-VIWzNJj2aZvmeZPUi8ONVIKc_syuT6UPZHYqDS3MxnNe1bFTN9YIev6BdTqVk59_HMDA7Y8xijHkzZsG__7_aO_zmhPgH33qLig</recordid><startdate>20190902</startdate><enddate>20190902</enddate><creator>Fujino, Naoya</creator><creator>Brand, Oliver J</creator><creator>Morgan, David J</creator><creator>Fujimori, Toshifumi</creator><creator>Grabiec, Aleksander M</creator><creator>Jagger, Christopher P</creator><creator>Maciewicz, Rose A</creator><creator>Yamada, Mitsuhiro</creator><creator>Itakura, Koji</creator><creator>Sugiura, Hisatoshi</creator><creator>Ichinose, Masakazu</creator><creator>Hussell, Tracy</creator><general>Rockefeller University Press</general><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1047-1001</orcidid><orcidid>https://orcid.org/0000-0001-7186-6141</orcidid><orcidid>https://orcid.org/0000-0002-5085-4093</orcidid><orcidid>https://orcid.org/0000-0002-5371-7828</orcidid></search><sort><creationdate>20190902</creationdate><title>Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases</title><author>Fujino, Naoya ; Brand, Oliver J ; Morgan, David J ; Fujimori, Toshifumi ; Grabiec, Aleksander M ; Jagger, Christopher P ; Maciewicz, Rose A ; Yamada, Mitsuhiro ; Itakura, Koji ; Sugiura, Hisatoshi ; Ichinose, Masakazu ; Hussell, Tracy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-71e37983b373e8a3483d0dd4aa9088d8fa23c9a04d4f296de601f80fd04940863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Aged</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Axl Receptor Tyrosine Kinase</topic><topic>Cell Cycle</topic><topic>Cell Proliferation</topic><topic>DNA - biosynthesis</topic><topic>Epithelium - pathology</topic><topic>Female</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Inflammation - enzymology</topic><topic>Inflammation - pathology</topic><topic>Lung - pathology</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Orthomyxoviridae - physiology</topic><topic>Orthomyxoviridae Infections - immunology</topic><topic>Orthomyxoviridae Infections - virology</topic><topic>Proto-Oncogene Proteins - deficiency</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Pulmonary Disease, Chronic Obstructive - enzymology</topic><topic>Pulmonary Disease, Chronic Obstructive - pathology</topic><topic>Re-Epithelialization</topic><topic>Receptor Protein-Tyrosine Kinases - deficiency</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Trachea - pathology</topic><topic>Trans-Activators - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujino, Naoya</creatorcontrib><creatorcontrib>Brand, Oliver J</creatorcontrib><creatorcontrib>Morgan, David J</creatorcontrib><creatorcontrib>Fujimori, Toshifumi</creatorcontrib><creatorcontrib>Grabiec, Aleksander M</creatorcontrib><creatorcontrib>Jagger, Christopher P</creatorcontrib><creatorcontrib>Maciewicz, Rose A</creatorcontrib><creatorcontrib>Yamada, Mitsuhiro</creatorcontrib><creatorcontrib>Itakura, Koji</creatorcontrib><creatorcontrib>Sugiura, Hisatoshi</creatorcontrib><creatorcontrib>Ichinose, Masakazu</creatorcontrib><creatorcontrib>Hussell, Tracy</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujino, Naoya</au><au>Brand, Oliver J</au><au>Morgan, David J</au><au>Fujimori, Toshifumi</au><au>Grabiec, Aleksander M</au><au>Jagger, Christopher P</au><au>Maciewicz, Rose A</au><au>Yamada, Mitsuhiro</au><au>Itakura, Koji</au><au>Sugiura, Hisatoshi</au><au>Ichinose, Masakazu</au><au>Hussell, Tracy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2019-09-02</date><risdate>2019</risdate><volume>216</volume><issue>9</issue><spage>2184</spage><epage>2201</epage><pages>2184-2201</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Epithelial cell proliferation, division, and differentiation are critical for barrier repair following inflammation, but the initial trigger for this process is unknown. Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal cell expansion, cell cycle reentry, and symmetrical cell division. Furthermore, once the pool of tracheal basal cells has expanded, silencing of Axl is required for their differentiation. Genetic depletion of Axl triggers asymmetrical cell division, leading to epithelial differentiation and ciliated cell regeneration. 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| subjects | Aged Animals Apoptosis Axl Receptor Tyrosine Kinase Cell Cycle Cell Proliferation DNA - biosynthesis Epithelium - pathology Female Homeostasis Humans Inflammation - enzymology Inflammation - pathology Lung - pathology Male Mice, Inbred C57BL Orthomyxoviridae - physiology Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - virology Proto-Oncogene Proteins - deficiency Proto-Oncogene Proteins - metabolism Pulmonary Disease, Chronic Obstructive - enzymology Pulmonary Disease, Chronic Obstructive - pathology Re-Epithelialization Receptor Protein-Tyrosine Kinases - deficiency Receptor Protein-Tyrosine Kinases - metabolism Trachea - pathology Trans-Activators - metabolism |
| title | Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases |
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