Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis
BackgroundThe aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS).MethodsILC1, ILC2 and ILC3 cells were...
Gespeichert in:
| Veröffentlicht in: | Annals of the rheumatic diseases 2015-09, Vol.74 (9), p.1739-1747 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1747 |
|---|---|
| container_issue | 9 |
| container_start_page | 1739 |
| container_title | Annals of the rheumatic diseases |
| container_volume | 74 |
| creator | Ciccia, Francesco Guggino, Giuliana Rizzo, Aroldo Saieva, Laura Peralta, Sergio Giardina, AnnaRita Cannizzaro, Alessandra Sireci, Guido De Leo, Giacomo Alessandro, Riccardo Triolo, Giovanni |
| description | BackgroundThe aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS).MethodsILC1, ILC2 and ILC3 cells were determined and characterised by confocal microscopy and flow cytometry in ileal and BM biopsies, in peripheral blood (PB) and SF mononuclear cells obtained from patients with AS and controls. Mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1), IL-7, IL-15 and aggregates of lymphoid tissue inducer cells (LTi) were evaluated by immunohistochemistry. The in vitro ability of epithelial cells in driving the differentiation of ILC3 and the effect of tumour necrosis factor inhibitors (TNFi) on the frequency of ILC3 and the expression of MADCAM1 were also assessed.ResultsILC3 characterised as Lyn−RORc−Tbet+ NKp44+ cells were significantly expanded in the gut, SF and BM of patients with AS compared with controls, produced high levels of IL-17 and IL-22 and expressed α4β7. MADcAM1 was overexpressed in BM and ileal high endothelial venules. IL-7 was significantly increased in AS gut, especially in the context of Paneth cells, and accompanied by the presence of aggregates of c-kit/IL-7R+ cells (LTi). In in vitro experiments, epithelial cells from patients with AS actively induced differentiation of ILC3 from LTi. TNFi efficacy was accompanied by a significant decrease in the percentage of intestinal and circulating ILC3 and in the expression of MADCAM1.ConclusionsGut-derived IL-17+ and IL-22+ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints. |
| doi_str_mv | 10.1136/annrheumdis-2014-206323 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1808690113</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4008713061</sourcerecordid><originalsourceid>FETCH-LOGICAL-b466t-e74d4abecfad7648be96002e76125459ea684f7ad7726c2a294377c4f31cdabe3</originalsourceid><addsrcrecordid>eNqNkc1u1DAUhS0EokPhFcASGxYN-G_seIkqfiqNxKasIye-aTwktrETSp6KV8RhWoTYwMb2tb9zrnwPQi8oeU0pl2-M92mAZbIuV4xQURbJGX-AdlTIeqvIQ7QjhPBKaKnO0JOcj6UkNa0fozO214QpTXbox_UaAXPsvDcz4HGd4hCcxR2MY8YxBbt0zt_gq0NFFTbebifGsEmA4XssF2CLGM8D4Jtlvrg_R0guDpDMiNsxBHuB8-rDN1fqflxKg82qDR7wZFIKtzj0OJrZgZ8zvnXzUIAv6xjy1jzH4O06utnlp-hRb8YMz-72c_T5_bvry4_V4dOHq8u3h6oVUs4VKGGFaaHrjVVS1C1oSQgDJSnbi70GI2vRq_KomOyYYVpwpTrRc9rZouPn6NXJt4zg6wJ5biaXt6EYD2HJDa1JLTUpYfwbVYRLXfNf6Mu_0GNYki8fKZRSmhKqZaHUiepSyDlB38TkypjWhpJmi7_5I_5mi785xV-Uz-_8l3YC-1t3n3cB2Alop-N_u_4EgPTAPQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1777910196</pqid></control><display><type>article</type><title>Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis</title><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><creator>Ciccia, Francesco ; Guggino, Giuliana ; Rizzo, Aroldo ; Saieva, Laura ; Peralta, Sergio ; Giardina, AnnaRita ; Cannizzaro, Alessandra ; Sireci, Guido ; De Leo, Giacomo ; Alessandro, Riccardo ; Triolo, Giovanni</creator><creatorcontrib>Ciccia, Francesco ; Guggino, Giuliana ; Rizzo, Aroldo ; Saieva, Laura ; Peralta, Sergio ; Giardina, AnnaRita ; Cannizzaro, Alessandra ; Sireci, Guido ; De Leo, Giacomo ; Alessandro, Riccardo ; Triolo, Giovanni</creatorcontrib><description>BackgroundThe aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS).MethodsILC1, ILC2 and ILC3 cells were determined and characterised by confocal microscopy and flow cytometry in ileal and BM biopsies, in peripheral blood (PB) and SF mononuclear cells obtained from patients with AS and controls. Mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1), IL-7, IL-15 and aggregates of lymphoid tissue inducer cells (LTi) were evaluated by immunohistochemistry. The in vitro ability of epithelial cells in driving the differentiation of ILC3 and the effect of tumour necrosis factor inhibitors (TNFi) on the frequency of ILC3 and the expression of MADCAM1 were also assessed.ResultsILC3 characterised as Lyn−RORc−Tbet+ NKp44+ cells were significantly expanded in the gut, SF and BM of patients with AS compared with controls, produced high levels of IL-17 and IL-22 and expressed α4β7. MADcAM1 was overexpressed in BM and ileal high endothelial venules. IL-7 was significantly increased in AS gut, especially in the context of Paneth cells, and accompanied by the presence of aggregates of c-kit/IL-7R+ cells (LTi). In in vitro experiments, epithelial cells from patients with AS actively induced differentiation of ILC3 from LTi. TNFi efficacy was accompanied by a significant decrease in the percentage of intestinal and circulating ILC3 and in the expression of MADCAM1.ConclusionsGut-derived IL-17+ and IL-22+ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints.</description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2014-206323</identifier><identifier>PMID: 25902790</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>England: Elsevier Limited</publisher><subject>Adolescent ; Adult ; Aged ; Antigens ; Biopsy ; Bone marrow ; Bone Marrow - immunology ; Case-Control Studies ; Cell Adhesion Molecules ; Cytokines ; Female ; Gene expression ; Humans ; Ileum - immunology ; Ileum - pathology ; Immunoglobulins - metabolism ; Immunology ; Inflammation ; Interleukin-15 - immunology ; Interleukin-17 - immunology ; Interleukin-22 ; Interleukin-7 - immunology ; Interleukins - immunology ; Intestinal Mucosa - immunology ; Lymphocytes ; Lymphocytes - immunology ; Male ; Microscopy, Confocal ; Middle Aged ; Mucoproteins - metabolism ; Natural Cytotoxicity Triggering Receptor 2 ; Small intestine ; Spondylitis, Ankylosing - immunology ; Synovial Fluid - immunology ; Tumor necrosis factor-TNF ; Young Adult</subject><ispartof>Annals of the rheumatic diseases, 2015-09, Vol.74 (9), p.1739-1747</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><rights>Copyright: 2015 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b466t-e74d4abecfad7648be96002e76125459ea684f7ad7726c2a294377c4f31cdabe3</citedby><cites>FETCH-LOGICAL-b466t-e74d4abecfad7648be96002e76125459ea684f7ad7726c2a294377c4f31cdabe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/74/9/1739.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/74/9/1739.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,776,780,3183,23550,27901,27902,77343,77374</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25902790$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ciccia, Francesco</creatorcontrib><creatorcontrib>Guggino, Giuliana</creatorcontrib><creatorcontrib>Rizzo, Aroldo</creatorcontrib><creatorcontrib>Saieva, Laura</creatorcontrib><creatorcontrib>Peralta, Sergio</creatorcontrib><creatorcontrib>Giardina, AnnaRita</creatorcontrib><creatorcontrib>Cannizzaro, Alessandra</creatorcontrib><creatorcontrib>Sireci, Guido</creatorcontrib><creatorcontrib>De Leo, Giacomo</creatorcontrib><creatorcontrib>Alessandro, Riccardo</creatorcontrib><creatorcontrib>Triolo, Giovanni</creatorcontrib><title>Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis</title><title>Annals of the rheumatic diseases</title><addtitle>Ann Rheum Dis</addtitle><description>BackgroundThe aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS).MethodsILC1, ILC2 and ILC3 cells were determined and characterised by confocal microscopy and flow cytometry in ileal and BM biopsies, in peripheral blood (PB) and SF mononuclear cells obtained from patients with AS and controls. Mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1), IL-7, IL-15 and aggregates of lymphoid tissue inducer cells (LTi) were evaluated by immunohistochemistry. The in vitro ability of epithelial cells in driving the differentiation of ILC3 and the effect of tumour necrosis factor inhibitors (TNFi) on the frequency of ILC3 and the expression of MADCAM1 were also assessed.ResultsILC3 characterised as Lyn−RORc−Tbet+ NKp44+ cells were significantly expanded in the gut, SF and BM of patients with AS compared with controls, produced high levels of IL-17 and IL-22 and expressed α4β7. MADcAM1 was overexpressed in BM and ileal high endothelial venules. IL-7 was significantly increased in AS gut, especially in the context of Paneth cells, and accompanied by the presence of aggregates of c-kit/IL-7R+ cells (LTi). In in vitro experiments, epithelial cells from patients with AS actively induced differentiation of ILC3 from LTi. TNFi efficacy was accompanied by a significant decrease in the percentage of intestinal and circulating ILC3 and in the expression of MADCAM1.ConclusionsGut-derived IL-17+ and IL-22+ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antigens</subject><subject>Biopsy</subject><subject>Bone marrow</subject><subject>Bone Marrow - immunology</subject><subject>Case-Control Studies</subject><subject>Cell Adhesion Molecules</subject><subject>Cytokines</subject><subject>Female</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Ileum - immunology</subject><subject>Ileum - pathology</subject><subject>Immunoglobulins - metabolism</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Interleukin-15 - immunology</subject><subject>Interleukin-17 - immunology</subject><subject>Interleukin-22</subject><subject>Interleukin-7 - immunology</subject><subject>Interleukins - immunology</subject><subject>Intestinal Mucosa - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes - immunology</subject><subject>Male</subject><subject>Microscopy, Confocal</subject><subject>Middle Aged</subject><subject>Mucoproteins - metabolism</subject><subject>Natural Cytotoxicity Triggering Receptor 2</subject><subject>Small intestine</subject><subject>Spondylitis, Ankylosing - immunology</subject><subject>Synovial Fluid - immunology</subject><subject>Tumor necrosis factor-TNF</subject><subject>Young Adult</subject><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkc1u1DAUhS0EokPhFcASGxYN-G_seIkqfiqNxKasIye-aTwktrETSp6KV8RhWoTYwMb2tb9zrnwPQi8oeU0pl2-M92mAZbIuV4xQURbJGX-AdlTIeqvIQ7QjhPBKaKnO0JOcj6UkNa0fozO214QpTXbox_UaAXPsvDcz4HGd4hCcxR2MY8YxBbt0zt_gq0NFFTbebifGsEmA4XssF2CLGM8D4Jtlvrg_R0guDpDMiNsxBHuB8-rDN1fqflxKg82qDR7wZFIKtzj0OJrZgZ8zvnXzUIAv6xjy1jzH4O06utnlp-hRb8YMz-72c_T5_bvry4_V4dOHq8u3h6oVUs4VKGGFaaHrjVVS1C1oSQgDJSnbi70GI2vRq_KomOyYYVpwpTrRc9rZouPn6NXJt4zg6wJ5biaXt6EYD2HJDa1JLTUpYfwbVYRLXfNf6Mu_0GNYki8fKZRSmhKqZaHUiepSyDlB38TkypjWhpJmi7_5I_5mi785xV-Uz-_8l3YC-1t3n3cB2Alop-N_u_4EgPTAPQ</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Ciccia, Francesco</creator><creator>Guggino, Giuliana</creator><creator>Rizzo, Aroldo</creator><creator>Saieva, Laura</creator><creator>Peralta, Sergio</creator><creator>Giardina, AnnaRita</creator><creator>Cannizzaro, Alessandra</creator><creator>Sireci, Guido</creator><creator>De Leo, Giacomo</creator><creator>Alessandro, Riccardo</creator><creator>Triolo, Giovanni</creator><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</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>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20150901</creationdate><title>Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis</title><author>Ciccia, Francesco ; Guggino, Giuliana ; Rizzo, Aroldo ; Saieva, Laura ; Peralta, Sergio ; Giardina, AnnaRita ; Cannizzaro, Alessandra ; Sireci, Guido ; De Leo, Giacomo ; Alessandro, Riccardo ; Triolo, Giovanni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b466t-e74d4abecfad7648be96002e76125459ea684f7ad7726c2a294377c4f31cdabe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antigens</topic><topic>Biopsy</topic><topic>Bone marrow</topic><topic>Bone Marrow - immunology</topic><topic>Case-Control Studies</topic><topic>Cell Adhesion Molecules</topic><topic>Cytokines</topic><topic>Female</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Ileum - immunology</topic><topic>Ileum - pathology</topic><topic>Immunoglobulins - metabolism</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Interleukin-15 - immunology</topic><topic>Interleukin-17 - immunology</topic><topic>Interleukin-22</topic><topic>Interleukin-7 - immunology</topic><topic>Interleukins - immunology</topic><topic>Intestinal Mucosa - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes - immunology</topic><topic>Male</topic><topic>Microscopy, Confocal</topic><topic>Middle Aged</topic><topic>Mucoproteins - metabolism</topic><topic>Natural Cytotoxicity Triggering Receptor 2</topic><topic>Small intestine</topic><topic>Spondylitis, Ankylosing - immunology</topic><topic>Synovial Fluid - immunology</topic><topic>Tumor necrosis factor-TNF</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ciccia, Francesco</creatorcontrib><creatorcontrib>Guggino, Giuliana</creatorcontrib><creatorcontrib>Rizzo, Aroldo</creatorcontrib><creatorcontrib>Saieva, Laura</creatorcontrib><creatorcontrib>Peralta, Sergio</creatorcontrib><creatorcontrib>Giardina, AnnaRita</creatorcontrib><creatorcontrib>Cannizzaro, Alessandra</creatorcontrib><creatorcontrib>Sireci, Guido</creatorcontrib><creatorcontrib>De Leo, Giacomo</creatorcontrib><creatorcontrib>Alessandro, Riccardo</creatorcontrib><creatorcontrib>Triolo, Giovanni</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>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</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)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Family Health Database (Proquest)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Science Database (ProQuest)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ciccia, Francesco</au><au>Guggino, Giuliana</au><au>Rizzo, Aroldo</au><au>Saieva, Laura</au><au>Peralta, Sergio</au><au>Giardina, AnnaRita</au><au>Cannizzaro, Alessandra</au><au>Sireci, Guido</au><au>De Leo, Giacomo</au><au>Alessandro, Riccardo</au><au>Triolo, Giovanni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis</atitle><jtitle>Annals of the rheumatic diseases</jtitle><addtitle>Ann Rheum Dis</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>74</volume><issue>9</issue><spage>1739</spage><epage>1747</epage><pages>1739-1747</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract>BackgroundThe aim of the study was to better characterise the immunological origin and the behaviour of interleukin (IL)-23-responsive innate lymphoid cells (ILCs) in the gut, synovial fluid (SF) and bone marrow (BM) of patients with ankylosing spondylitis (AS).MethodsILC1, ILC2 and ILC3 cells were determined and characterised by confocal microscopy and flow cytometry in ileal and BM biopsies, in peripheral blood (PB) and SF mononuclear cells obtained from patients with AS and controls. Mucosal vascular addressin cell adhesion molecule 1 (MADCAM-1), IL-7, IL-15 and aggregates of lymphoid tissue inducer cells (LTi) were evaluated by immunohistochemistry. The in vitro ability of epithelial cells in driving the differentiation of ILC3 and the effect of tumour necrosis factor inhibitors (TNFi) on the frequency of ILC3 and the expression of MADCAM1 were also assessed.ResultsILC3 characterised as Lyn−RORc−Tbet+ NKp44+ cells were significantly expanded in the gut, SF and BM of patients with AS compared with controls, produced high levels of IL-17 and IL-22 and expressed α4β7. MADcAM1 was overexpressed in BM and ileal high endothelial venules. IL-7 was significantly increased in AS gut, especially in the context of Paneth cells, and accompanied by the presence of aggregates of c-kit/IL-7R+ cells (LTi). In in vitro experiments, epithelial cells from patients with AS actively induced differentiation of ILC3 from LTi. TNFi efficacy was accompanied by a significant decrease in the percentage of intestinal and circulating ILC3 and in the expression of MADCAM1.ConclusionsGut-derived IL-17+ and IL-22+ILC3 are expanded in the peripheral blood, SF and inflamed BM of patients with AS, suggesting the presence of an active homing axis between the gut and the inflamed sacroiliac joints.</abstract><cop>England</cop><pub>Elsevier Limited</pub><pmid>25902790</pmid><doi>10.1136/annrheumdis-2014-206323</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0003-4967 |
| ispartof | Annals of the rheumatic diseases, 2015-09, Vol.74 (9), p.1739-1747 |
| issn | 0003-4967 1468-2060 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1808690113 |
| source | MEDLINE; BMJ Journals - NESLi2 |
| subjects | Adolescent Adult Aged Antigens Biopsy Bone marrow Bone Marrow - immunology Case-Control Studies Cell Adhesion Molecules Cytokines Female Gene expression Humans Ileum - immunology Ileum - pathology Immunoglobulins - metabolism Immunology Inflammation Interleukin-15 - immunology Interleukin-17 - immunology Interleukin-22 Interleukin-7 - immunology Interleukins - immunology Intestinal Mucosa - immunology Lymphocytes Lymphocytes - immunology Male Microscopy, Confocal Middle Aged Mucoproteins - metabolism Natural Cytotoxicity Triggering Receptor 2 Small intestine Spondylitis, Ankylosing - immunology Synovial Fluid - immunology Tumor necrosis factor-TNF Young Adult |
| title | Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T06%3A58%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Type%203%20innate%20lymphoid%20cells%20producing%20IL-17%20and%20IL-22%20are%20expanded%20in%20the%20gut,%20in%20the%20peripheral%20blood,%20synovial%20fluid%20and%20bone%20marrow%20of%20patients%20with%20ankylosing%20spondylitis&rft.jtitle=Annals%20of%20the%20rheumatic%20diseases&rft.au=Ciccia,%20Francesco&rft.date=2015-09-01&rft.volume=74&rft.issue=9&rft.spage=1739&rft.epage=1747&rft.pages=1739-1747&rft.issn=0003-4967&rft.eissn=1468-2060&rft.coden=ARDIAO&rft_id=info:doi/10.1136/annrheumdis-2014-206323&rft_dat=%3Cproquest_cross%3E4008713061%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1777910196&rft_id=info:pmid/25902790&rfr_iscdi=true |