Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of...
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| Veröffentlicht in: | Mucosal immunology 2020-01, Vol.13 (1), p.86-95 |
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| creator | Ogasawara, Noriko Poposki, Julie A. Klingler, Aiko I. Tan, Bruce K. Hulse, Kathryn E. Stevens, Whitney W. Peters, Anju T. Grammer, Leslie C. Welch, Kevin C. Smith, Stephanie S. Conley, David B. Raviv, Joseph R. Soroosh, Pejman Takano, Ken-ichi Himi, Tetsuo Kern, Robert C. Schleimer, Robert P. Kato, Atsushi |
| description | Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including T
H
2 cells in NPs. The co-culture of NP-derived ILC2s and T
H
2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP. |
| doi_str_mv | 10.1038/s41385-019-0215-8 |
| format | Article |
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H
2 cells in NPs. The co-culture of NP-derived ILC2s and T
H
2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.</description><identifier>ISSN: 1933-0219</identifier><identifier>EISSN: 1935-3456</identifier><identifier>DOI: 10.1038/s41385-019-0215-8</identifier><identifier>PMID: 31641233</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Allergology ; Antibodies ; Biomedical and Life Sciences ; Biomedicine ; CD45 antigen ; Cell culture ; Cells, Cultured ; Chronic Disease ; Cytokines ; Cytokines - metabolism ; Female ; Gastroenterology ; Helper cells ; Humans ; Immunity, Innate ; Immunology ; Inflammation ; Inflammation - immunology ; Lymphocytes - immunology ; Lymphocytes T ; Lymphoid cells ; Male ; Middle Aged ; Monoclonal antibodies ; Nasal Polyps - immunology ; NF-κB protein ; Peripheral blood ; Polyps ; RANK Ligand - metabolism ; Rhinitis ; Rhinitis - immunology ; Rhinosinusitis ; Sinusitis ; Sinusitis - immunology ; Th2 Cells - immunology ; Th2 Cells - metabolism ; Thymic stromal lymphopoietin ; Thymus ; TRANCE protein ; Tumor necrosis factor ; Young Adult</subject><ispartof>Mucosal immunology, 2020-01, Vol.13 (1), p.86-95</ispartof><rights>Society for Mucosal Immunology 2019</rights><rights>Copyright Nature Publishing Group Jan 2020</rights><rights>Society for Mucosal Immunology 2019.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-f21b4bfc2c27c1cc3e4aabe54b6e72f11180c4d92b78c5997ecf42ca453d73323</citedby><cites>FETCH-LOGICAL-c498t-f21b4bfc2c27c1cc3e4aabe54b6e72f11180c4d92b78c5997ecf42ca453d73323</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31641233$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ogasawara, Noriko</creatorcontrib><creatorcontrib>Poposki, Julie A.</creatorcontrib><creatorcontrib>Klingler, Aiko I.</creatorcontrib><creatorcontrib>Tan, Bruce K.</creatorcontrib><creatorcontrib>Hulse, Kathryn E.</creatorcontrib><creatorcontrib>Stevens, Whitney W.</creatorcontrib><creatorcontrib>Peters, Anju T.</creatorcontrib><creatorcontrib>Grammer, Leslie C.</creatorcontrib><creatorcontrib>Welch, Kevin C.</creatorcontrib><creatorcontrib>Smith, Stephanie S.</creatorcontrib><creatorcontrib>Conley, David B.</creatorcontrib><creatorcontrib>Raviv, Joseph R.</creatorcontrib><creatorcontrib>Soroosh, Pejman</creatorcontrib><creatorcontrib>Takano, Ken-ichi</creatorcontrib><creatorcontrib>Himi, Tetsuo</creatorcontrib><creatorcontrib>Kern, Robert C.</creatorcontrib><creatorcontrib>Schleimer, Robert P.</creatorcontrib><creatorcontrib>Kato, Atsushi</creatorcontrib><title>Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps</title><title>Mucosal immunology</title><addtitle>Mucosal Immunol</addtitle><addtitle>Mucosal Immunol</addtitle><description>Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including T
H
2 cells in NPs. The co-culture of NP-derived ILC2s and T
H
2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Allergology</subject><subject>Antibodies</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CD45 antigen</subject><subject>Cell culture</subject><subject>Cells, Cultured</subject><subject>Chronic Disease</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Helper cells</subject><subject>Humans</subject><subject>Immunity, Innate</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Inflammation - immunology</subject><subject>Lymphocytes - immunology</subject><subject>Lymphocytes T</subject><subject>Lymphoid cells</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Monoclonal antibodies</subject><subject>Nasal Polyps - immunology</subject><subject>NF-κB protein</subject><subject>Peripheral blood</subject><subject>Polyps</subject><subject>RANK Ligand - metabolism</subject><subject>Rhinitis</subject><subject>Rhinitis - immunology</subject><subject>Rhinosinusitis</subject><subject>Sinusitis</subject><subject>Sinusitis - immunology</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - metabolism</subject><subject>Thymic stromal lymphopoietin</subject><subject>Thymus</subject><subject>TRANCE protein</subject><subject>Tumor necrosis factor</subject><subject>Young Adult</subject><issn>1933-0219</issn><issn>1935-3456</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUtv1TAQhSNERR_wA9ggS2zYhHr8iO0NUnUFpeKqSBWsLcdxel0ldrCTVvff49tbykOiK491vjkzo1NVrwG_B0zlaWZAJa8xqBoT4LV8Vh2BorymjDfP72u6U9RhdZzzDcYNxpy-qA4pNAwIpUfV7VUcHIo9ujq7_FKvkcnIoCnOLszeDMiHbrEu7YCL9YrUo-u8mV2H5u3kECl6P5hxNLOPoXyQ3aQYvEVp40PMPizZzz6jOz9vUDC5OE5x2E75ZXXQmyG7Vw_vSfX908dvq8_1-uv5xepsXVum5Fz3BFrW9pZYIixYSx0zpnWctY0TpAcAiS3rFGmFtFwp4WzPiDWM005QSuhJ9WHvOy1t2d2Ws5IZ9JT8aNJWR-P130rwG30db3WjQEjFisG7B4MUfywuz3r02bphMMHFJWtCsQRB5f2st_-gN3FJoZynCRMcU2CNeJKipCwNmKtCwZ6yKeacXP-4MmC9y17vs9cle73LXsvS8-bPWx87foVdALIHcpHCtUu_R__f9SeG7LnU</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Ogasawara, Noriko</creator><creator>Poposki, Julie A.</creator><creator>Klingler, Aiko I.</creator><creator>Tan, Bruce K.</creator><creator>Hulse, Kathryn E.</creator><creator>Stevens, Whitney W.</creator><creator>Peters, Anju T.</creator><creator>Grammer, Leslie C.</creator><creator>Welch, Kevin C.</creator><creator>Smith, Stephanie S.</creator><creator>Conley, David B.</creator><creator>Raviv, Joseph R.</creator><creator>Soroosh, Pejman</creator><creator>Takano, Ken-ichi</creator><creator>Himi, Tetsuo</creator><creator>Kern, Robert C.</creator><creator>Schleimer, Robert P.</creator><creator>Kato, Atsushi</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200101</creationdate><title>Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps</title><author>Ogasawara, Noriko ; Poposki, Julie A. ; Klingler, Aiko I. ; Tan, Bruce K. ; Hulse, Kathryn E. ; Stevens, Whitney W. ; Peters, Anju T. ; Grammer, Leslie C. ; Welch, Kevin C. ; Smith, Stephanie S. ; Conley, David B. ; Raviv, Joseph R. ; Soroosh, Pejman ; Takano, Ken-ichi ; Himi, Tetsuo ; Kern, Robert C. ; Schleimer, Robert P. ; Kato, Atsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-f21b4bfc2c27c1cc3e4aabe54b6e72f11180c4d92b78c5997ecf42ca453d73323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Allergology</topic><topic>Antibodies</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>CD45 antigen</topic><topic>Cell culture</topic><topic>Cells, Cultured</topic><topic>Chronic Disease</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Helper cells</topic><topic>Humans</topic><topic>Immunity, Innate</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Inflammation - immunology</topic><topic>Lymphocytes - immunology</topic><topic>Lymphocytes T</topic><topic>Lymphoid cells</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Monoclonal antibodies</topic><topic>Nasal Polyps - immunology</topic><topic>NF-κB protein</topic><topic>Peripheral blood</topic><topic>Polyps</topic><topic>RANK Ligand - metabolism</topic><topic>Rhinitis</topic><topic>Rhinitis - immunology</topic><topic>Rhinosinusitis</topic><topic>Sinusitis</topic><topic>Sinusitis - immunology</topic><topic>Th2 Cells - immunology</topic><topic>Th2 Cells - metabolism</topic><topic>Thymic stromal lymphopoietin</topic><topic>Thymus</topic><topic>TRANCE protein</topic><topic>Tumor necrosis factor</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ogasawara, Noriko</creatorcontrib><creatorcontrib>Poposki, Julie A.</creatorcontrib><creatorcontrib>Klingler, Aiko I.</creatorcontrib><creatorcontrib>Tan, Bruce K.</creatorcontrib><creatorcontrib>Hulse, Kathryn E.</creatorcontrib><creatorcontrib>Stevens, Whitney W.</creatorcontrib><creatorcontrib>Peters, Anju T.</creatorcontrib><creatorcontrib>Grammer, Leslie C.</creatorcontrib><creatorcontrib>Welch, Kevin C.</creatorcontrib><creatorcontrib>Smith, Stephanie S.</creatorcontrib><creatorcontrib>Conley, David B.</creatorcontrib><creatorcontrib>Raviv, Joseph R.</creatorcontrib><creatorcontrib>Soroosh, Pejman</creatorcontrib><creatorcontrib>Takano, Ken-ichi</creatorcontrib><creatorcontrib>Himi, Tetsuo</creatorcontrib><creatorcontrib>Kern, Robert C.</creatorcontrib><creatorcontrib>Schleimer, Robert P.</creatorcontrib><creatorcontrib>Kato, Atsushi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Mucosal immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ogasawara, Noriko</au><au>Poposki, Julie A.</au><au>Klingler, Aiko I.</au><au>Tan, Bruce K.</au><au>Hulse, Kathryn E.</au><au>Stevens, Whitney W.</au><au>Peters, Anju T.</au><au>Grammer, Leslie C.</au><au>Welch, Kevin C.</au><au>Smith, Stephanie S.</au><au>Conley, David B.</au><au>Raviv, Joseph R.</au><au>Soroosh, Pejman</au><au>Takano, Ken-ichi</au><au>Himi, Tetsuo</au><au>Kern, Robert C.</au><au>Schleimer, Robert P.</au><au>Kato, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps</atitle><jtitle>Mucosal immunology</jtitle><stitle>Mucosal Immunol</stitle><addtitle>Mucosal Immunol</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>13</volume><issue>1</issue><spage>86</spage><epage>95</epage><pages>86-95</pages><issn>1933-0219</issn><eissn>1935-3456</eissn><abstract>Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including T
H
2 cells in NPs. The co-culture of NP-derived ILC2s and T
H
2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>31641233</pmid><doi>10.1038/s41385-019-0215-8</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 1933-0219 1935-3456 |
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| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6917894 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Aged Aged, 80 and over Allergology Antibodies Biomedical and Life Sciences Biomedicine CD45 antigen Cell culture Cells, Cultured Chronic Disease Cytokines Cytokines - metabolism Female Gastroenterology Helper cells Humans Immunity, Innate Immunology Inflammation Inflammation - immunology Lymphocytes - immunology Lymphocytes T Lymphoid cells Male Middle Aged Monoclonal antibodies Nasal Polyps - immunology NF-κB protein Peripheral blood Polyps RANK Ligand - metabolism Rhinitis Rhinitis - immunology Rhinosinusitis Sinusitis Sinusitis - immunology Th2 Cells - immunology Th2 Cells - metabolism Thymic stromal lymphopoietin Thymus TRANCE protein Tumor necrosis factor Young Adult |
| title | Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps |
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