Increased proportions of functionally impaired regulatory T cell subsets in systemic sclerosis
Abstract Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 pro...
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| Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2017-11, Vol.184, p.54-62 |
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| creator | Ugor, Emese Simon, Diána Almanzar, Giovanni Pap, Ramóna Najbauer, József Németh, Péter Balogh, Péter Prelog, Martina Czirják, László Berki, Tímea |
| description | Abstract Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127– Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis. Increased CD62L+ Treg cells were present in all SSc subgroups. The production of immunosuppressive cytokines by both CD127– and CD62L+ Tregs was diminished. We observed reduced methylation of Treg specific FOXP3 enhancer regions, and elevated FOXP3 gene expression in active SSc cases with negative correlation in the frequency of CD62L+IL-10+ Tregs. Our data indicate an inappropriate distribution and cytokine production of Treg cells in early form SSc. |
| doi_str_mv | 10.1016/j.clim.2017.05.013 |
| format | Article |
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Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127– Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis. Increased CD62L+ Treg cells were present in all SSc subgroups. The production of immunosuppressive cytokines by both CD127– and CD62L+ Tregs was diminished. We observed reduced methylation of Treg specific FOXP3 enhancer regions, and elevated FOXP3 gene expression in active SSc cases with negative correlation in the frequency of CD62L+IL-10+ Tregs. Our data indicate an inappropriate distribution and cytokine production of Treg cells in early form SSc.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1016/j.clim.2017.05.013</identifier><identifier>PMID: 28522286</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Allergy and Immunology ; Antibodies, Antinuclear - immunology ; DNA Methylation ; Epigenesis, Genetic ; Epigenetic regulation ; Female ; Forkhead Transcription Factors - genetics ; FOXP3 ; Gene Expression ; Gene Expression Regulation ; Humans ; IL-10 ; Interleukin-10 - immunology ; Middle Aged ; Nuclear Proteins - immunology ; Promoter Regions, Genetic ; Pulmonary Fibrosis - etiology ; Pulmonary Fibrosis - immunology ; Regulatory T cells ; RNA Polymerase III - immunology ; Scleroderma, Diffuse - complications ; Scleroderma, Diffuse - immunology ; Scleroderma, Limited - complications ; Scleroderma, Limited - immunology ; Scleroderma, Systemic - complications ; Scleroderma, Systemic - immunology ; Systemic sclerosis ; T-Lymphocyte Subsets - immunology ; T-Lymphocytes, Regulatory - immunology ; TGF-β ; Transforming Growth Factor beta - immunology</subject><ispartof>Clinical immunology (Orlando, Fla.), 2017-11, Vol.184, p.54-62</ispartof><rights>Elsevier Inc.</rights><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c460t-9704c956b6af2a87087a36725182cbb3df9a3d6d81c7fe7ed6f029766a788b083</citedby><cites>FETCH-LOGICAL-c460t-9704c956b6af2a87087a36725182cbb3df9a3d6d81c7fe7ed6f029766a788b083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clim.2017.05.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28522286$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ugor, Emese</creatorcontrib><creatorcontrib>Simon, Diána</creatorcontrib><creatorcontrib>Almanzar, Giovanni</creatorcontrib><creatorcontrib>Pap, Ramóna</creatorcontrib><creatorcontrib>Najbauer, József</creatorcontrib><creatorcontrib>Németh, Péter</creatorcontrib><creatorcontrib>Balogh, Péter</creatorcontrib><creatorcontrib>Prelog, Martina</creatorcontrib><creatorcontrib>Czirják, László</creatorcontrib><creatorcontrib>Berki, Tímea</creatorcontrib><title>Increased proportions of functionally impaired regulatory T cell subsets in systemic sclerosis</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Abstract Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127– Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis. Increased CD62L+ Treg cells were present in all SSc subgroups. The production of immunosuppressive cytokines by both CD127– and CD62L+ Tregs was diminished. We observed reduced methylation of Treg specific FOXP3 enhancer regions, and elevated FOXP3 gene expression in active SSc cases with negative correlation in the frequency of CD62L+IL-10+ Tregs. Our data indicate an inappropriate distribution and cytokine production of Treg cells in early form SSc.</description><subject>Adult</subject><subject>Aged</subject><subject>Allergy and Immunology</subject><subject>Antibodies, Antinuclear - immunology</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic regulation</subject><subject>Female</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>FOXP3</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>IL-10</subject><subject>Interleukin-10 - immunology</subject><subject>Middle Aged</subject><subject>Nuclear Proteins - immunology</subject><subject>Promoter Regions, Genetic</subject><subject>Pulmonary Fibrosis - etiology</subject><subject>Pulmonary Fibrosis - immunology</subject><subject>Regulatory T cells</subject><subject>RNA Polymerase III - immunology</subject><subject>Scleroderma, Diffuse - complications</subject><subject>Scleroderma, Diffuse - immunology</subject><subject>Scleroderma, Limited - complications</subject><subject>Scleroderma, Limited - immunology</subject><subject>Scleroderma, Systemic - complications</subject><subject>Scleroderma, Systemic - immunology</subject><subject>Systemic sclerosis</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>TGF-β</subject><subject>Transforming Growth Factor beta - immunology</subject><issn>1521-6616</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2L1TAUxYsozof-Ay4kSzev3qQvHwURZFBnYMCF49aQpreSZ9o8c9uB_vemvKcLF65yA79zuOfcqnrFoebA1dtD7WMYawFc1yBr4M2T6pJLwXcaGvn0PCvF1UV1RXQAACmEel5dCFMGYdRl9f1u8hkdYc-OOR1TnkOaiKWBDcvkt4-LcWVhPLqQC5TxxxLdnPLKHpjHGBktHeFMLEyMVppxDJ6Rj5gTBXpRPRtcJHx5fq-rb58-Ptzc7u6_fL67-XC_83sF867VsPetVJ1yg3BGg9GuUVpIboTvuqYfWtf0qjfc6wE19moA0WqlnDamA9NcV29OviXErwVptmOgbT03YVrI8hYKted7KKg4ob5sSBkHe8xhdHm1HOzWqz3YrVe79WpB2tJrEb0--y_diP1fyZ8iC_DuBGBJ-RgwW_IBJ499qc3Ptk_h__7v_5EXZArexZ-4Ih3SksshSg5LwoL9ul12OyxXDUipZfMbeaafZw</recordid><startdate>20171101</startdate><enddate>20171101</enddate><creator>Ugor, Emese</creator><creator>Simon, Diána</creator><creator>Almanzar, Giovanni</creator><creator>Pap, Ramóna</creator><creator>Najbauer, József</creator><creator>Németh, Péter</creator><creator>Balogh, Péter</creator><creator>Prelog, Martina</creator><creator>Czirják, László</creator><creator>Berki, Tímea</creator><general>Elsevier Inc</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></search><sort><creationdate>20171101</creationdate><title>Increased proportions of functionally impaired regulatory T cell subsets in systemic sclerosis</title><author>Ugor, Emese ; Simon, Diána ; Almanzar, Giovanni ; Pap, Ramóna ; Najbauer, József ; Németh, Péter ; Balogh, Péter ; Prelog, Martina ; Czirják, László ; Berki, Tímea</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c460t-9704c956b6af2a87087a36725182cbb3df9a3d6d81c7fe7ed6f029766a788b083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Allergy and Immunology</topic><topic>Antibodies, Antinuclear - immunology</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetic regulation</topic><topic>Female</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>FOXP3</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>IL-10</topic><topic>Interleukin-10 - immunology</topic><topic>Middle Aged</topic><topic>Nuclear Proteins - immunology</topic><topic>Promoter Regions, Genetic</topic><topic>Pulmonary Fibrosis - etiology</topic><topic>Pulmonary Fibrosis - immunology</topic><topic>Regulatory T cells</topic><topic>RNA Polymerase III - immunology</topic><topic>Scleroderma, Diffuse - complications</topic><topic>Scleroderma, Diffuse - immunology</topic><topic>Scleroderma, Limited - complications</topic><topic>Scleroderma, Limited - immunology</topic><topic>Scleroderma, Systemic - complications</topic><topic>Scleroderma, Systemic - immunology</topic><topic>Systemic sclerosis</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>TGF-β</topic><topic>Transforming Growth Factor beta - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ugor, Emese</creatorcontrib><creatorcontrib>Simon, Diána</creatorcontrib><creatorcontrib>Almanzar, Giovanni</creatorcontrib><creatorcontrib>Pap, Ramóna</creatorcontrib><creatorcontrib>Najbauer, József</creatorcontrib><creatorcontrib>Németh, Péter</creatorcontrib><creatorcontrib>Balogh, Péter</creatorcontrib><creatorcontrib>Prelog, Martina</creatorcontrib><creatorcontrib>Czirják, László</creatorcontrib><creatorcontrib>Berki, Tímea</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><jtitle>Clinical immunology (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ugor, Emese</au><au>Simon, Diána</au><au>Almanzar, Giovanni</au><au>Pap, Ramóna</au><au>Najbauer, József</au><au>Németh, Péter</au><au>Balogh, Péter</au><au>Prelog, Martina</au><au>Czirják, László</au><au>Berki, Tímea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased proportions of functionally impaired regulatory T cell subsets in systemic sclerosis</atitle><jtitle>Clinical immunology (Orlando, Fla.)</jtitle><addtitle>Clin Immunol</addtitle><date>2017-11-01</date><risdate>2017</risdate><volume>184</volume><spage>54</spage><epage>62</epage><pages>54-62</pages><issn>1521-6616</issn><eissn>1521-7035</eissn><abstract>Abstract Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127– Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis. Increased CD62L+ Treg cells were present in all SSc subgroups. The production of immunosuppressive cytokines by both CD127– and CD62L+ Tregs was diminished. We observed reduced methylation of Treg specific FOXP3 enhancer regions, and elevated FOXP3 gene expression in active SSc cases with negative correlation in the frequency of CD62L+IL-10+ Tregs. Our data indicate an inappropriate distribution and cytokine production of Treg cells in early form SSc.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28522286</pmid><doi>10.1016/j.clim.2017.05.013</doi><tpages>9</tpages></addata></record> |
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| ispartof | Clinical immunology (Orlando, Fla.), 2017-11, Vol.184, p.54-62 |
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| subjects | Adult Aged Allergy and Immunology Antibodies, Antinuclear - immunology DNA Methylation Epigenesis, Genetic Epigenetic regulation Female Forkhead Transcription Factors - genetics FOXP3 Gene Expression Gene Expression Regulation Humans IL-10 Interleukin-10 - immunology Middle Aged Nuclear Proteins - immunology Promoter Regions, Genetic Pulmonary Fibrosis - etiology Pulmonary Fibrosis - immunology Regulatory T cells RNA Polymerase III - immunology Scleroderma, Diffuse - complications Scleroderma, Diffuse - immunology Scleroderma, Limited - complications Scleroderma, Limited - immunology Scleroderma, Systemic - complications Scleroderma, Systemic - immunology Systemic sclerosis T-Lymphocyte Subsets - immunology T-Lymphocytes, Regulatory - immunology TGF-β Transforming Growth Factor beta - immunology |
| title | Increased proportions of functionally impaired regulatory T cell subsets in systemic sclerosis |
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