Expansion of intestinal CD4+CD25high Treg cells in patients with ankylosing spondylitis: A putative role for interleukin‐10 in preventing intestinal Th17 response
Objective Subclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25high T cells (Treg cells) and to evaluate Treg cell–related cytokines (interleukin‐2 [IL‐2], transforming growth facto...
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| Veröffentlicht in: | Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2010-12, Vol.62 (12), p.3625-3634 |
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| creator | Ciccia, Francesco Accardo‐Palumbo, Antonina Giardina, AnnaRita Di Maggio, Piera Principato, Alfonso Bombardieri, Michele Rizzo, Aroldo Alessandro, Riccardo Ferrante, Angelo Principe, Simona Peralta, Sergio Conte, Francesco Drago, Sandro Craxì, Antonio De Leo, Giacomo Triolo, Giovanni |
| description | Objective
Subclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25high T cells (Treg cells) and to evaluate Treg cell–related cytokines (interleukin‐2 [IL‐2], transforming growth factor β [TGFβ], and IL‐10) and transcription factors (FoxP3 and STAT‐5) in the ileum of patients with AS.
Methods
Quantitative gene expression analysis, by reverse transcriptase–polymerase chain reaction, of Treg‐related cytokines (IL‐2, TGFβ, and IL‐10) and transcription factors (STAT‐5 and FoxP3) was performed on ileal biopsy specimens from 18 patients with AS, 15 patients with active Crohn's disease (CD), and 15 healthy subjects. Tissue and circulating Treg cells were also analyzed by flow cytometry.
Results
A significant up‐regulation of IL‐2, TGFβ, FoxP3, STAT‐5, and IL‐10 transcripts in the terminal ileum of AS patients displaying chronic ileal inflammation was observed. Flow cytometric analysis of Treg cells showed significant peripheral expansion in both patients with AS and chronic inflammation and patients with CD (mean ± SD 1.08 ± 0.4% and 1.05 ± 0.3%, respectively) as compared with healthy subjects (0.25 ± 0.12%) (P < 0.05). Interestingly, a 5‐fold increase in the proportion of Treg cells was observed in the gut of patients with AS (5 ± 3%) as compared with healthy subjects (1.2 ± 0.4%) (P < 0.001), with 70–80% of these cells also producing IL‐10. In vitro studies showed that blocking IL‐10 was sufficient to induce Th17 polarization on lamina propria mononuclear cells isolated from AS patients.
Conclusion
Our findings provide the first evidence that an active Treg cell response, mainly dominated by IL‐10 production, occurs in the gut of AS patients and is probably responsible for the absence of a clear Th17 polarization in the ileum of AS patients. |
| doi_str_mv | 10.1002/art.27699 |
| format | Article |
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Subclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25high T cells (Treg cells) and to evaluate Treg cell–related cytokines (interleukin‐2 [IL‐2], transforming growth factor β [TGFβ], and IL‐10) and transcription factors (FoxP3 and STAT‐5) in the ileum of patients with AS.
Methods
Quantitative gene expression analysis, by reverse transcriptase–polymerase chain reaction, of Treg‐related cytokines (IL‐2, TGFβ, and IL‐10) and transcription factors (STAT‐5 and FoxP3) was performed on ileal biopsy specimens from 18 patients with AS, 15 patients with active Crohn's disease (CD), and 15 healthy subjects. Tissue and circulating Treg cells were also analyzed by flow cytometry.
Results
A significant up‐regulation of IL‐2, TGFβ, FoxP3, STAT‐5, and IL‐10 transcripts in the terminal ileum of AS patients displaying chronic ileal inflammation was observed. Flow cytometric analysis of Treg cells showed significant peripheral expansion in both patients with AS and chronic inflammation and patients with CD (mean ± SD 1.08 ± 0.4% and 1.05 ± 0.3%, respectively) as compared with healthy subjects (0.25 ± 0.12%) (P < 0.05). Interestingly, a 5‐fold increase in the proportion of Treg cells was observed in the gut of patients with AS (5 ± 3%) as compared with healthy subjects (1.2 ± 0.4%) (P < 0.001), with 70–80% of these cells also producing IL‐10. In vitro studies showed that blocking IL‐10 was sufficient to induce Th17 polarization on lamina propria mononuclear cells isolated from AS patients.
Conclusion
Our findings provide the first evidence that an active Treg cell response, mainly dominated by IL‐10 production, occurs in the gut of AS patients and is probably responsible for the absence of a clear Th17 polarization in the ileum of AS patients.</description><identifier>ISSN: 0004-3591</identifier><identifier>ISSN: 2326-5191</identifier><identifier>EISSN: 1529-0131</identifier><identifier>EISSN: 2326-5205</identifier><identifier>DOI: 10.1002/art.27699</identifier><identifier>CODEN: ARHEAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Biological and medical sciences ; Diseases of the osteoarticular system ; Diseases of the spine ; Inflammatory joint diseases ; Medical sciences</subject><ispartof>Arthritis & rheumatology (Hoboken, N.J.), 2010-12, Vol.62 (12), p.3625-3634</ispartof><rights>Copyright © 2010 by the American College of Rheumatology</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fart.27699$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fart.27699$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23716140$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Ciccia, Francesco</creatorcontrib><creatorcontrib>Accardo‐Palumbo, Antonina</creatorcontrib><creatorcontrib>Giardina, AnnaRita</creatorcontrib><creatorcontrib>Di Maggio, Piera</creatorcontrib><creatorcontrib>Principato, Alfonso</creatorcontrib><creatorcontrib>Bombardieri, Michele</creatorcontrib><creatorcontrib>Rizzo, Aroldo</creatorcontrib><creatorcontrib>Alessandro, Riccardo</creatorcontrib><creatorcontrib>Ferrante, Angelo</creatorcontrib><creatorcontrib>Principe, Simona</creatorcontrib><creatorcontrib>Peralta, Sergio</creatorcontrib><creatorcontrib>Conte, Francesco</creatorcontrib><creatorcontrib>Drago, Sandro</creatorcontrib><creatorcontrib>Craxì, Antonio</creatorcontrib><creatorcontrib>De Leo, Giacomo</creatorcontrib><creatorcontrib>Triolo, Giovanni</creatorcontrib><title>Expansion of intestinal CD4+CD25high Treg cells in patients with ankylosing spondylitis: A putative role for interleukin‐10 in preventing intestinal Th17 response</title><title>Arthritis & rheumatology (Hoboken, N.J.)</title><description>Objective
Subclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25high T cells (Treg cells) and to evaluate Treg cell–related cytokines (interleukin‐2 [IL‐2], transforming growth factor β [TGFβ], and IL‐10) and transcription factors (FoxP3 and STAT‐5) in the ileum of patients with AS.
Methods
Quantitative gene expression analysis, by reverse transcriptase–polymerase chain reaction, of Treg‐related cytokines (IL‐2, TGFβ, and IL‐10) and transcription factors (STAT‐5 and FoxP3) was performed on ileal biopsy specimens from 18 patients with AS, 15 patients with active Crohn's disease (CD), and 15 healthy subjects. Tissue and circulating Treg cells were also analyzed by flow cytometry.
Results
A significant up‐regulation of IL‐2, TGFβ, FoxP3, STAT‐5, and IL‐10 transcripts in the terminal ileum of AS patients displaying chronic ileal inflammation was observed. Flow cytometric analysis of Treg cells showed significant peripheral expansion in both patients with AS and chronic inflammation and patients with CD (mean ± SD 1.08 ± 0.4% and 1.05 ± 0.3%, respectively) as compared with healthy subjects (0.25 ± 0.12%) (P < 0.05). Interestingly, a 5‐fold increase in the proportion of Treg cells was observed in the gut of patients with AS (5 ± 3%) as compared with healthy subjects (1.2 ± 0.4%) (P < 0.001), with 70–80% of these cells also producing IL‐10. In vitro studies showed that blocking IL‐10 was sufficient to induce Th17 polarization on lamina propria mononuclear cells isolated from AS patients.
Conclusion
Our findings provide the first evidence that an active Treg cell response, mainly dominated by IL‐10 production, occurs in the gut of AS patients and is probably responsible for the absence of a clear Th17 polarization in the ileum of AS patients.</description><subject>Biological and medical sciences</subject><subject>Diseases of the osteoarticular system</subject><subject>Diseases of the spine</subject><subject>Inflammatory joint diseases</subject><subject>Medical sciences</subject><issn>0004-3591</issn><issn>2326-5191</issn><issn>1529-0131</issn><issn>2326-5205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNpNkctOGzEUhq0KpIa0i76BpYpVNeTYZ25mF4WrhFQJhfXIM2MnTlzP1J4A2fEIPARPxpPgBIRYHR_58-df-gn5xeCEAfCJ9MMJL3IhvpERy7hIgCE7ICMASBPMBPtOjkJYxZVjhiPycv7YSxdM52inqXGDCoNx0tLZWfpndsazpVks6dyrBW2UtSEitJeDUW4I9MEMSyrdemu7YNyChr5z7daawYRTOqX9ZojkvaK-s4rqzu_93qrN2rjXp2cGe5tX99G2e__l-_mSFdSrnTGoH-RQSxvUz485JncX5_PZVXLz9_J6Nr1JeoYokrYsSwGYacjbVreAqqhrnUKGHDHHWvMCRaNRi5QLXSvN61SWSoFsQJSZxjH5_e7tffd_E6NUq27jY5xQsSLNyxwKyCN1_EHJ0EirvXSNCVXvzT_ptxXHguUshchN3rkHY9X2855BtWuqik1V-6aq6e18f8A31NSLdw</recordid><startdate>201012</startdate><enddate>201012</enddate><creator>Ciccia, Francesco</creator><creator>Accardo‐Palumbo, Antonina</creator><creator>Giardina, AnnaRita</creator><creator>Di Maggio, Piera</creator><creator>Principato, Alfonso</creator><creator>Bombardieri, Michele</creator><creator>Rizzo, Aroldo</creator><creator>Alessandro, Riccardo</creator><creator>Ferrante, Angelo</creator><creator>Principe, Simona</creator><creator>Peralta, Sergio</creator><creator>Conte, Francesco</creator><creator>Drago, Sandro</creator><creator>Craxì, Antonio</creator><creator>De Leo, Giacomo</creator><creator>Triolo, Giovanni</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>IQODW</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TM</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>201012</creationdate><title>Expansion of intestinal CD4+CD25high Treg cells in patients with ankylosing spondylitis: A putative role for interleukin‐10 in preventing intestinal Th17 response</title><author>Ciccia, Francesco ; Accardo‐Palumbo, Antonina ; Giardina, AnnaRita ; Di Maggio, Piera ; Principato, Alfonso ; Bombardieri, Michele ; Rizzo, Aroldo ; Alessandro, Riccardo ; Ferrante, Angelo ; Principe, Simona ; Peralta, Sergio ; Conte, Francesco ; Drago, Sandro ; Craxì, Antonio ; De Leo, Giacomo ; Triolo, Giovanni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1339-d8889035f06ddfd03e7bbf405323363bf2739cf3f9429fbef2b4a8ee0ac0985f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Biological and medical sciences</topic><topic>Diseases of the osteoarticular system</topic><topic>Diseases of the spine</topic><topic>Inflammatory joint diseases</topic><topic>Medical sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ciccia, Francesco</creatorcontrib><creatorcontrib>Accardo‐Palumbo, Antonina</creatorcontrib><creatorcontrib>Giardina, AnnaRita</creatorcontrib><creatorcontrib>Di Maggio, Piera</creatorcontrib><creatorcontrib>Principato, Alfonso</creatorcontrib><creatorcontrib>Bombardieri, Michele</creatorcontrib><creatorcontrib>Rizzo, Aroldo</creatorcontrib><creatorcontrib>Alessandro, Riccardo</creatorcontrib><creatorcontrib>Ferrante, Angelo</creatorcontrib><creatorcontrib>Principe, Simona</creatorcontrib><creatorcontrib>Peralta, Sergio</creatorcontrib><creatorcontrib>Conte, Francesco</creatorcontrib><creatorcontrib>Drago, Sandro</creatorcontrib><creatorcontrib>Craxì, Antonio</creatorcontrib><creatorcontrib>De Leo, Giacomo</creatorcontrib><creatorcontrib>Triolo, Giovanni</creatorcontrib><collection>Pascal-Francis</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ciccia, Francesco</au><au>Accardo‐Palumbo, Antonina</au><au>Giardina, AnnaRita</au><au>Di Maggio, Piera</au><au>Principato, Alfonso</au><au>Bombardieri, Michele</au><au>Rizzo, Aroldo</au><au>Alessandro, Riccardo</au><au>Ferrante, Angelo</au><au>Principe, Simona</au><au>Peralta, Sergio</au><au>Conte, Francesco</au><au>Drago, Sandro</au><au>Craxì, Antonio</au><au>De Leo, Giacomo</au><au>Triolo, Giovanni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expansion of intestinal CD4+CD25high Treg cells in patients with ankylosing spondylitis: A putative role for interleukin‐10 in preventing intestinal Th17 response</atitle><jtitle>Arthritis & rheumatology (Hoboken, N.J.)</jtitle><date>2010-12</date><risdate>2010</risdate><volume>62</volume><issue>12</issue><spage>3625</spage><epage>3634</epage><pages>3625-3634</pages><issn>0004-3591</issn><issn>2326-5191</issn><eissn>1529-0131</eissn><eissn>2326-5205</eissn><coden>ARHEAW</coden><abstract>Objective
Subclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25high T cells (Treg cells) and to evaluate Treg cell–related cytokines (interleukin‐2 [IL‐2], transforming growth factor β [TGFβ], and IL‐10) and transcription factors (FoxP3 and STAT‐5) in the ileum of patients with AS.
Methods
Quantitative gene expression analysis, by reverse transcriptase–polymerase chain reaction, of Treg‐related cytokines (IL‐2, TGFβ, and IL‐10) and transcription factors (STAT‐5 and FoxP3) was performed on ileal biopsy specimens from 18 patients with AS, 15 patients with active Crohn's disease (CD), and 15 healthy subjects. Tissue and circulating Treg cells were also analyzed by flow cytometry.
Results
A significant up‐regulation of IL‐2, TGFβ, FoxP3, STAT‐5, and IL‐10 transcripts in the terminal ileum of AS patients displaying chronic ileal inflammation was observed. Flow cytometric analysis of Treg cells showed significant peripheral expansion in both patients with AS and chronic inflammation and patients with CD (mean ± SD 1.08 ± 0.4% and 1.05 ± 0.3%, respectively) as compared with healthy subjects (0.25 ± 0.12%) (P < 0.05). Interestingly, a 5‐fold increase in the proportion of Treg cells was observed in the gut of patients with AS (5 ± 3%) as compared with healthy subjects (1.2 ± 0.4%) (P < 0.001), with 70–80% of these cells also producing IL‐10. In vitro studies showed that blocking IL‐10 was sufficient to induce Th17 polarization on lamina propria mononuclear cells isolated from AS patients.
Conclusion
Our findings provide the first evidence that an active Treg cell response, mainly dominated by IL‐10 production, occurs in the gut of AS patients and is probably responsible for the absence of a clear Th17 polarization in the ileum of AS patients.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><doi>10.1002/art.27699</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biological and medical sciences Diseases of the osteoarticular system Diseases of the spine Inflammatory joint diseases Medical sciences |
| title | Expansion of intestinal CD4+CD25high Treg cells in patients with ankylosing spondylitis: A putative role for interleukin‐10 in preventing intestinal Th17 response |
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