Human CD8+CD25 +CD127 low regulatory T cells: microRNA signature and impact on TGF‐β and IL‐10 expression
Regulatory T cells (Tregs) are central for maintaining immune balance and their dysfunction drives the expansion of critical immunologic disorders. During the past decade, microRNAs (miRNAs) have emerged as potent regulators of gene expression among which immune‐related genes and their immunomodulat...
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| Veröffentlicht in: | Journal of cellular physiology 2019-10, Vol.234 (10), p.17459-17472 |
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| creator | Rouas, Redouane Merimi, Makram Najar, Mehdi El Zein, Nabil Fayyad‐Kazan, Mohammad Berehab, Mimoune Agha, Douaa Bron, Dominique Burny, Arsene Rachidi, Walid Badran, Bassam Lewalle, Philippe Fayyad‐Kazan, Hussein |
| description | Regulatory T cells (Tregs) are central for maintaining immune balance and their dysfunction drives the expansion of critical immunologic disorders. During the past decade, microRNAs (miRNAs) have emerged as potent regulators of gene expression among which immune‐related genes and their immunomodulatory properties have been associated with different immune‐based diseases. The miRNA signature of human peripheral blood (PB) CD8+CD25
+CD127
low Tregs has not been described yet. We thus identified, using TaqMan low‐density array (TLDA) technique followed by individual quantitative real‐time polymerase chain reaction (qRT‐PCR) confirmation, 14 miRNAs, among which 12 were downregulated whereas two were upregulated in CD8
+CD25
+CD127
low Tregs in comparison to CD8
+CD25
− T cells. In the next step, microRNA Data Integration Portal (mirDIP) was used to identify potential miRNA target sites in the 3′‐untranslated region (3′‐UTR) of key Treg cell‐immunomodulatory genes with a special focus on interleukin 10 (IL‐10) and transforming growth factor β (TGF‐β). Having identified potential miR target sites in the 3′‐UTR of IL‐10 (miR‐27b‐3p and miR‐340‐5p) and TGF‐β (miR‐330‐3p), we showed through transfection and transduction assays that the overexpression of two underexpressed miRNAs, miR‐27b‐3p and miR‐340‐5p, downregulated IL‐10 expression upon targeting its 3′‐UTR. Similarly, overexpression of miR‐330‐3p negatively regulated TGF‐β expression. These results highlighted an important impact of the CD8
+ Treg mirnome on the expression of genes with significant implication on immunosuppression. These observations could help in better understanding the mechanism(s) orchestrating Treg immunosuppressive function toward unraveling new targets for treating autoimmune pathologies and cancer.
A microRNA (miRNA) signature for peripheral blood CD8+ Tregs and the impact of differentially expressed miRs on interleukin 10 and transforming growth factor β. |
| doi_str_mv | 10.1002/jcp.28367 |
| format | Article |
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+CD127
low Tregs has not been described yet. We thus identified, using TaqMan low‐density array (TLDA) technique followed by individual quantitative real‐time polymerase chain reaction (qRT‐PCR) confirmation, 14 miRNAs, among which 12 were downregulated whereas two were upregulated in CD8
+CD25
+CD127
low Tregs in comparison to CD8
+CD25
− T cells. In the next step, microRNA Data Integration Portal (mirDIP) was used to identify potential miRNA target sites in the 3′‐untranslated region (3′‐UTR) of key Treg cell‐immunomodulatory genes with a special focus on interleukin 10 (IL‐10) and transforming growth factor β (TGF‐β). Having identified potential miR target sites in the 3′‐UTR of IL‐10 (miR‐27b‐3p and miR‐340‐5p) and TGF‐β (miR‐330‐3p), we showed through transfection and transduction assays that the overexpression of two underexpressed miRNAs, miR‐27b‐3p and miR‐340‐5p, downregulated IL‐10 expression upon targeting its 3′‐UTR. Similarly, overexpression of miR‐330‐3p negatively regulated TGF‐β expression. These results highlighted an important impact of the CD8
+ Treg mirnome on the expression of genes with significant implication on immunosuppression. These observations could help in better understanding the mechanism(s) orchestrating Treg immunosuppressive function toward unraveling new targets for treating autoimmune pathologies and cancer.
A microRNA (miRNA) signature for peripheral blood CD8+ Tregs and the impact of differentially expressed miRs on interleukin 10 and transforming growth factor β.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.28367</identifier><identifier>PMID: 30805923</identifier><language>eng</language><publisher>United States</publisher><subject>human Tregs ; IL‐10 ; micro‐RNA ; TGF‐β</subject><ispartof>Journal of cellular physiology, 2019-10, Vol.234 (10), p.17459-17472</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1707-dbff0d97ceafef8b62ea4b703a8f9b591d322541fd0aa7559001da2ee0bdb4973</citedby><cites>FETCH-LOGICAL-c1707-dbff0d97ceafef8b62ea4b703a8f9b591d322541fd0aa7559001da2ee0bdb4973</cites><orcidid>0000-0001-8442-1619 ; 0000-0002-3465-4630</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.28367$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.28367$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30805923$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rouas, Redouane</creatorcontrib><creatorcontrib>Merimi, Makram</creatorcontrib><creatorcontrib>Najar, Mehdi</creatorcontrib><creatorcontrib>El Zein, Nabil</creatorcontrib><creatorcontrib>Fayyad‐Kazan, Mohammad</creatorcontrib><creatorcontrib>Berehab, Mimoune</creatorcontrib><creatorcontrib>Agha, Douaa</creatorcontrib><creatorcontrib>Bron, Dominique</creatorcontrib><creatorcontrib>Burny, Arsene</creatorcontrib><creatorcontrib>Rachidi, Walid</creatorcontrib><creatorcontrib>Badran, Bassam</creatorcontrib><creatorcontrib>Lewalle, Philippe</creatorcontrib><creatorcontrib>Fayyad‐Kazan, Hussein</creatorcontrib><title>Human CD8+CD25 +CD127 low regulatory T cells: microRNA signature and impact on TGF‐β and IL‐10 expression</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>Regulatory T cells (Tregs) are central for maintaining immune balance and their dysfunction drives the expansion of critical immunologic disorders. During the past decade, microRNAs (miRNAs) have emerged as potent regulators of gene expression among which immune‐related genes and their immunomodulatory properties have been associated with different immune‐based diseases. The miRNA signature of human peripheral blood (PB) CD8+CD25
+CD127
low Tregs has not been described yet. We thus identified, using TaqMan low‐density array (TLDA) technique followed by individual quantitative real‐time polymerase chain reaction (qRT‐PCR) confirmation, 14 miRNAs, among which 12 were downregulated whereas two were upregulated in CD8
+CD25
+CD127
low Tregs in comparison to CD8
+CD25
− T cells. In the next step, microRNA Data Integration Portal (mirDIP) was used to identify potential miRNA target sites in the 3′‐untranslated region (3′‐UTR) of key Treg cell‐immunomodulatory genes with a special focus on interleukin 10 (IL‐10) and transforming growth factor β (TGF‐β). Having identified potential miR target sites in the 3′‐UTR of IL‐10 (miR‐27b‐3p and miR‐340‐5p) and TGF‐β (miR‐330‐3p), we showed through transfection and transduction assays that the overexpression of two underexpressed miRNAs, miR‐27b‐3p and miR‐340‐5p, downregulated IL‐10 expression upon targeting its 3′‐UTR. Similarly, overexpression of miR‐330‐3p negatively regulated TGF‐β expression. These results highlighted an important impact of the CD8
+ Treg mirnome on the expression of genes with significant implication on immunosuppression. These observations could help in better understanding the mechanism(s) orchestrating Treg immunosuppressive function toward unraveling new targets for treating autoimmune pathologies and cancer.
A microRNA (miRNA) signature for peripheral blood CD8+ Tregs and the impact of differentially expressed miRs on interleukin 10 and transforming growth factor β.</description><subject>human Tregs</subject><subject>IL‐10</subject><subject>micro‐RNA</subject><subject>TGF‐β</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kEtOwzAURS0EoqUwYAPIQxBK--wkdcysSukHVYBQGUdO4lRB-WEnKp2xBNbCQlgEK8FtCjMmz0_PR0e6F6FzAn0CQAcvUdWnnj1kB6hLgDPLGbr0EHXNH7G465AOOtH6BQA4t-1j1LHBA5dTu4uKWZOLAvtj79ofUxebSSjDWbnGSq6aTNSl2uAljmSW6Rucp5Eqn-5HWKerQtSNklgUMU7zSkQ1Lgu8nE6-3z--Pnfn-cLsBLB8q5TUOi2LU3SUiEzLs_3bQ8-T26U_sxYP07k_WlgRYcCsOEwSiDmLpEhk4oVDKoUTMrCFl_DQ5SS2KTW5khiEYK7LAUgsqJQQxqHDmd1Dl623UuVrI3Ud5KneZhCFLBsdUOINiQOeQwx61aImmdZKJkGl0lyoTUAg2NYbmHqDXb2GvdhrmzCX8R_526cBBi2wTjO5-d8U3PmPrfIHI2mEbQ</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Rouas, Redouane</creator><creator>Merimi, Makram</creator><creator>Najar, Mehdi</creator><creator>El Zein, Nabil</creator><creator>Fayyad‐Kazan, Mohammad</creator><creator>Berehab, Mimoune</creator><creator>Agha, Douaa</creator><creator>Bron, Dominique</creator><creator>Burny, Arsene</creator><creator>Rachidi, Walid</creator><creator>Badran, Bassam</creator><creator>Lewalle, Philippe</creator><creator>Fayyad‐Kazan, Hussein</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8442-1619</orcidid><orcidid>https://orcid.org/0000-0002-3465-4630</orcidid></search><sort><creationdate>201910</creationdate><title>Human CD8+CD25 +CD127 low regulatory T cells: microRNA signature and impact on TGF‐β and IL‐10 expression</title><author>Rouas, Redouane ; Merimi, Makram ; Najar, Mehdi ; El Zein, Nabil ; Fayyad‐Kazan, Mohammad ; Berehab, Mimoune ; Agha, Douaa ; Bron, Dominique ; Burny, Arsene ; Rachidi, Walid ; Badran, Bassam ; Lewalle, Philippe ; Fayyad‐Kazan, Hussein</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1707-dbff0d97ceafef8b62ea4b703a8f9b591d322541fd0aa7559001da2ee0bdb4973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>human Tregs</topic><topic>IL‐10</topic><topic>micro‐RNA</topic><topic>TGF‐β</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rouas, Redouane</creatorcontrib><creatorcontrib>Merimi, Makram</creatorcontrib><creatorcontrib>Najar, Mehdi</creatorcontrib><creatorcontrib>El Zein, Nabil</creatorcontrib><creatorcontrib>Fayyad‐Kazan, Mohammad</creatorcontrib><creatorcontrib>Berehab, Mimoune</creatorcontrib><creatorcontrib>Agha, Douaa</creatorcontrib><creatorcontrib>Bron, Dominique</creatorcontrib><creatorcontrib>Burny, Arsene</creatorcontrib><creatorcontrib>Rachidi, Walid</creatorcontrib><creatorcontrib>Badran, Bassam</creatorcontrib><creatorcontrib>Lewalle, Philippe</creatorcontrib><creatorcontrib>Fayyad‐Kazan, Hussein</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rouas, Redouane</au><au>Merimi, Makram</au><au>Najar, Mehdi</au><au>El Zein, Nabil</au><au>Fayyad‐Kazan, Mohammad</au><au>Berehab, Mimoune</au><au>Agha, Douaa</au><au>Bron, Dominique</au><au>Burny, Arsene</au><au>Rachidi, Walid</au><au>Badran, Bassam</au><au>Lewalle, Philippe</au><au>Fayyad‐Kazan, Hussein</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human CD8+CD25 +CD127 low regulatory T cells: microRNA signature and impact on TGF‐β and IL‐10 expression</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2019-10</date><risdate>2019</risdate><volume>234</volume><issue>10</issue><spage>17459</spage><epage>17472</epage><pages>17459-17472</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Regulatory T cells (Tregs) are central for maintaining immune balance and their dysfunction drives the expansion of critical immunologic disorders. During the past decade, microRNAs (miRNAs) have emerged as potent regulators of gene expression among which immune‐related genes and their immunomodulatory properties have been associated with different immune‐based diseases. The miRNA signature of human peripheral blood (PB) CD8+CD25
+CD127
low Tregs has not been described yet. We thus identified, using TaqMan low‐density array (TLDA) technique followed by individual quantitative real‐time polymerase chain reaction (qRT‐PCR) confirmation, 14 miRNAs, among which 12 were downregulated whereas two were upregulated in CD8
+CD25
+CD127
low Tregs in comparison to CD8
+CD25
− T cells. In the next step, microRNA Data Integration Portal (mirDIP) was used to identify potential miRNA target sites in the 3′‐untranslated region (3′‐UTR) of key Treg cell‐immunomodulatory genes with a special focus on interleukin 10 (IL‐10) and transforming growth factor β (TGF‐β). Having identified potential miR target sites in the 3′‐UTR of IL‐10 (miR‐27b‐3p and miR‐340‐5p) and TGF‐β (miR‐330‐3p), we showed through transfection and transduction assays that the overexpression of two underexpressed miRNAs, miR‐27b‐3p and miR‐340‐5p, downregulated IL‐10 expression upon targeting its 3′‐UTR. Similarly, overexpression of miR‐330‐3p negatively regulated TGF‐β expression. These results highlighted an important impact of the CD8
+ Treg mirnome on the expression of genes with significant implication on immunosuppression. These observations could help in better understanding the mechanism(s) orchestrating Treg immunosuppressive function toward unraveling new targets for treating autoimmune pathologies and cancer.
A microRNA (miRNA) signature for peripheral blood CD8+ Tregs and the impact of differentially expressed miRs on interleukin 10 and transforming growth factor β.</abstract><cop>United States</cop><pmid>30805923</pmid><doi>10.1002/jcp.28367</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-8442-1619</orcidid><orcidid>https://orcid.org/0000-0002-3465-4630</orcidid></addata></record> |
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| ispartof | Journal of cellular physiology, 2019-10, Vol.234 (10), p.17459-17472 |
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| language | eng |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | human Tregs IL‐10 micro‐RNA TGF‐β |
| title | Human CD8+CD25 +CD127 low regulatory T cells: microRNA signature and impact on TGF‐β and IL‐10 expression |
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