Increased levels of adipose tissue-resident Th17 cells in obesity associated with miR-326
•A higher frequency of CD4+IL-17A + T cells, RORC2 expression and miR-326 in adipose tissue from individuals with obesity.•Altered levels of proinflammatory cytokines in adipose tissue mononuclear cells from individuals with obesity in vitro.•High degree of FOXP3 methylation and low level of FOXP3 e...
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| Veröffentlicht in: | Immunology letters 2019-07, Vol.211, p.60-67 |
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| creator | Vega-Cárdenas, Mariela Uresti-Rivera, Edith E. Cortés-García, Juan D. Briones-Espinoza, Margarita Ruíz-Rodríguez, Víctor M. Reynaga-Hernández, Elizabeth Mendez-Mancilla, Alejandro Portales-Pérez, Diana P. |
| description | •A higher frequency of CD4+IL-17A + T cells, RORC2 expression and miR-326 in adipose tissue from individuals with obesity.•Altered levels of proinflammatory cytokines in adipose tissue mononuclear cells from individuals with obesity in vitro.•High degree of FOXP3 methylation and low level of FOXP3 expression in adipose tissue mononuclear cells from individuals with obesity.
miRNAs are important immune regulators in the control of the CD4 + T cells phenotype. miR-326 regulates the differentiation towards Th17 cells and the inhibition of miR-155 is associated with low levels of Treg cells. However, miRNAs expression and transcription factors associated with these lymphocyte subsets in obesity-induced adipose tissue inflammation is still unknown. The aim of this work was to identify Th17 cells in subcutaneous adipose tissue (SAT), proinflammatory cytokine production and their association with the miRNAs and transcription factors involved. We collected SAT samples obtained by lipoaspiration from individuals with normal weight, overweight and obesity. We obtained the stromal vascular fractions and then a Ficoll gradient was performed to obtain adipose tissue mononuclear cells (ATMC). Th17 cells were evaluated by flow cytometry and the expression of miR-326, miR-155, RORC2 and FOXP3 by qRT-PCR. We also analyzed cytokines from the supernatants of the ATMC culture and measured the FOXP3 methylation percentage by bisulfite conversion by PCR. According to the results, the frequency of Th17 cells and RORC2 expression was higher in individuals with obesity and associated with miR-326 expression. The ATMC from this group secreted a proinflammatory cytokine profile by in vitro assay. In contrast, lower levels of mRNA FOXP3 expression was detected in ATMC from individuals with obesity that correlated with methylation percentage of FOXP3 gene but no association with miR-155 was detected. Our results suggested that miR-326 participates in the polarization towards Th17 promoting the inflammatory state in the obesity-induced adipose tissue. |
| doi_str_mv | 10.1016/j.imlet.2019.05.010 |
| format | Article |
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miRNAs are important immune regulators in the control of the CD4 + T cells phenotype. miR-326 regulates the differentiation towards Th17 cells and the inhibition of miR-155 is associated with low levels of Treg cells. However, miRNAs expression and transcription factors associated with these lymphocyte subsets in obesity-induced adipose tissue inflammation is still unknown. The aim of this work was to identify Th17 cells in subcutaneous adipose tissue (SAT), proinflammatory cytokine production and their association with the miRNAs and transcription factors involved. We collected SAT samples obtained by lipoaspiration from individuals with normal weight, overweight and obesity. We obtained the stromal vascular fractions and then a Ficoll gradient was performed to obtain adipose tissue mononuclear cells (ATMC). Th17 cells were evaluated by flow cytometry and the expression of miR-326, miR-155, RORC2 and FOXP3 by qRT-PCR. We also analyzed cytokines from the supernatants of the ATMC culture and measured the FOXP3 methylation percentage by bisulfite conversion by PCR. According to the results, the frequency of Th17 cells and RORC2 expression was higher in individuals with obesity and associated with miR-326 expression. The ATMC from this group secreted a proinflammatory cytokine profile by in vitro assay. In contrast, lower levels of mRNA FOXP3 expression was detected in ATMC from individuals with obesity that correlated with methylation percentage of FOXP3 gene but no association with miR-155 was detected. Our results suggested that miR-326 participates in the polarization towards Th17 promoting the inflammatory state in the obesity-induced adipose tissue.</description><identifier>ISSN: 0165-2478</identifier><identifier>EISSN: 1879-0542</identifier><identifier>DOI: 10.1016/j.imlet.2019.05.010</identifier><identifier>PMID: 31136754</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adipose tissue ; Adipose Tissue - immunology ; Adult ; Cell Differentiation ; Cells, Cultured ; Female ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; FOXP3 methylation ; Gene Expression Regulation ; Humans ; Inflammation ; Lymphocyte Activation ; Male ; MicroRNAs - genetics ; Middle Aged ; miR-155 ; miR-326 ; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics ; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism ; Obesity ; Obesity - genetics ; Obesity - immunology ; T-Lymphocytes, Regulatory - immunology ; Th17 cells ; Th17 Cells - immunology ; Transcription factors ; Young Adult</subject><ispartof>Immunology letters, 2019-07, Vol.211, p.60-67</ispartof><rights>2019 European Federation of Immunological Societies</rights><rights>Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-f82f2c4a0d490e1a13327a0a52c875ecb2a7e4743ab51c2a5c1c4eceac1932963</citedby><cites>FETCH-LOGICAL-c359t-f82f2c4a0d490e1a13327a0a52c875ecb2a7e4743ab51c2a5c1c4eceac1932963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.imlet.2019.05.010$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31136754$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vega-Cárdenas, Mariela</creatorcontrib><creatorcontrib>Uresti-Rivera, Edith E.</creatorcontrib><creatorcontrib>Cortés-García, Juan D.</creatorcontrib><creatorcontrib>Briones-Espinoza, Margarita</creatorcontrib><creatorcontrib>Ruíz-Rodríguez, Víctor M.</creatorcontrib><creatorcontrib>Reynaga-Hernández, Elizabeth</creatorcontrib><creatorcontrib>Mendez-Mancilla, Alejandro</creatorcontrib><creatorcontrib>Portales-Pérez, Diana P.</creatorcontrib><title>Increased levels of adipose tissue-resident Th17 cells in obesity associated with miR-326</title><title>Immunology letters</title><addtitle>Immunol Lett</addtitle><description>•A higher frequency of CD4+IL-17A + T cells, RORC2 expression and miR-326 in adipose tissue from individuals with obesity.•Altered levels of proinflammatory cytokines in adipose tissue mononuclear cells from individuals with obesity in vitro.•High degree of FOXP3 methylation and low level of FOXP3 expression in adipose tissue mononuclear cells from individuals with obesity.
miRNAs are important immune regulators in the control of the CD4 + T cells phenotype. miR-326 regulates the differentiation towards Th17 cells and the inhibition of miR-155 is associated with low levels of Treg cells. However, miRNAs expression and transcription factors associated with these lymphocyte subsets in obesity-induced adipose tissue inflammation is still unknown. The aim of this work was to identify Th17 cells in subcutaneous adipose tissue (SAT), proinflammatory cytokine production and their association with the miRNAs and transcription factors involved. We collected SAT samples obtained by lipoaspiration from individuals with normal weight, overweight and obesity. We obtained the stromal vascular fractions and then a Ficoll gradient was performed to obtain adipose tissue mononuclear cells (ATMC). Th17 cells were evaluated by flow cytometry and the expression of miR-326, miR-155, RORC2 and FOXP3 by qRT-PCR. We also analyzed cytokines from the supernatants of the ATMC culture and measured the FOXP3 methylation percentage by bisulfite conversion by PCR. According to the results, the frequency of Th17 cells and RORC2 expression was higher in individuals with obesity and associated with miR-326 expression. The ATMC from this group secreted a proinflammatory cytokine profile by in vitro assay. In contrast, lower levels of mRNA FOXP3 expression was detected in ATMC from individuals with obesity that correlated with methylation percentage of FOXP3 gene but no association with miR-155 was detected. Our results suggested that miR-326 participates in the polarization towards Th17 promoting the inflammatory state in the obesity-induced adipose tissue.</description><subject>Adipose tissue</subject><subject>Adipose Tissue - immunology</subject><subject>Adult</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Female</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>FOXP3 methylation</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Lymphocyte Activation</subject><subject>Male</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>miR-155</subject><subject>miR-326</subject><subject>Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics</subject><subject>Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism</subject><subject>Obesity</subject><subject>Obesity - genetics</subject><subject>Obesity - immunology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Th17 cells</subject><subject>Th17 Cells - immunology</subject><subject>Transcription factors</subject><subject>Young Adult</subject><issn>0165-2478</issn><issn>1879-0542</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rGzEQhkVpqZ2PXxAIOvayW40-rN1DDyW0TSAQCOkhJyFrZ7HMfrgaOSH_vnKc5tjTwPC87wwPYxcgahCw-rqt4zhgrqWAthamFiA-sCU0tq2E0fIjWxbKVFLbZsFOiLZCgFFafWYLBaBW1ugle7yZQkJP2PEBn3AgPvfcd3E3E_IcifZYJaTY4ZT5wwYsDzgUKk58Xpd9fuGeaA7R51LxHPOGj_G-UnJ1xj71fiA8f5un7PfPHw9X19Xt3a-bq--3VVCmzVXfyF4G7UWnW4HgQSlpvfBGhsYaDGvpLWqrlV8bCNKbAEFjQB-gVbJdqVP25di7S_OfPVJ2Y6TDk37CeU9OSgWNtlbogqojGtJMlLB3uxRHn14cCHdw6rbu1ak7OHXCuOK0pC7fDuzXI3bvmX8SC_DtCBR9-BQxOQoRp4BdTBiy6-b43wN_Adj6iHo</recordid><startdate>201907</startdate><enddate>201907</enddate><creator>Vega-Cárdenas, Mariela</creator><creator>Uresti-Rivera, Edith E.</creator><creator>Cortés-García, Juan D.</creator><creator>Briones-Espinoza, Margarita</creator><creator>Ruíz-Rodríguez, Víctor M.</creator><creator>Reynaga-Hernández, Elizabeth</creator><creator>Mendez-Mancilla, Alejandro</creator><creator>Portales-Pérez, Diana P.</creator><general>Elsevier B.V</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>201907</creationdate><title>Increased levels of adipose tissue-resident Th17 cells in obesity associated with miR-326</title><author>Vega-Cárdenas, Mariela ; Uresti-Rivera, Edith E. ; Cortés-García, Juan D. ; Briones-Espinoza, Margarita ; Ruíz-Rodríguez, Víctor M. ; Reynaga-Hernández, Elizabeth ; Mendez-Mancilla, Alejandro ; Portales-Pérez, Diana P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-f82f2c4a0d490e1a13327a0a52c875ecb2a7e4743ab51c2a5c1c4eceac1932963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adipose tissue</topic><topic>Adipose Tissue - immunology</topic><topic>Adult</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Female</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>FOXP3 methylation</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Lymphocyte Activation</topic><topic>Male</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>miR-155</topic><topic>miR-326</topic><topic>Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics</topic><topic>Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism</topic><topic>Obesity</topic><topic>Obesity - genetics</topic><topic>Obesity - immunology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Th17 cells</topic><topic>Th17 Cells - immunology</topic><topic>Transcription factors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vega-Cárdenas, Mariela</creatorcontrib><creatorcontrib>Uresti-Rivera, Edith E.</creatorcontrib><creatorcontrib>Cortés-García, Juan D.</creatorcontrib><creatorcontrib>Briones-Espinoza, Margarita</creatorcontrib><creatorcontrib>Ruíz-Rodríguez, Víctor M.</creatorcontrib><creatorcontrib>Reynaga-Hernández, Elizabeth</creatorcontrib><creatorcontrib>Mendez-Mancilla, Alejandro</creatorcontrib><creatorcontrib>Portales-Pérez, Diana P.</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>Immunology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vega-Cárdenas, Mariela</au><au>Uresti-Rivera, Edith E.</au><au>Cortés-García, Juan D.</au><au>Briones-Espinoza, Margarita</au><au>Ruíz-Rodríguez, Víctor M.</au><au>Reynaga-Hernández, Elizabeth</au><au>Mendez-Mancilla, Alejandro</au><au>Portales-Pérez, Diana P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased levels of adipose tissue-resident Th17 cells in obesity associated with miR-326</atitle><jtitle>Immunology letters</jtitle><addtitle>Immunol Lett</addtitle><date>2019-07</date><risdate>2019</risdate><volume>211</volume><spage>60</spage><epage>67</epage><pages>60-67</pages><issn>0165-2478</issn><eissn>1879-0542</eissn><abstract>•A higher frequency of CD4+IL-17A + T cells, RORC2 expression and miR-326 in adipose tissue from individuals with obesity.•Altered levels of proinflammatory cytokines in adipose tissue mononuclear cells from individuals with obesity in vitro.•High degree of FOXP3 methylation and low level of FOXP3 expression in adipose tissue mononuclear cells from individuals with obesity.
miRNAs are important immune regulators in the control of the CD4 + T cells phenotype. miR-326 regulates the differentiation towards Th17 cells and the inhibition of miR-155 is associated with low levels of Treg cells. However, miRNAs expression and transcription factors associated with these lymphocyte subsets in obesity-induced adipose tissue inflammation is still unknown. The aim of this work was to identify Th17 cells in subcutaneous adipose tissue (SAT), proinflammatory cytokine production and their association with the miRNAs and transcription factors involved. We collected SAT samples obtained by lipoaspiration from individuals with normal weight, overweight and obesity. We obtained the stromal vascular fractions and then a Ficoll gradient was performed to obtain adipose tissue mononuclear cells (ATMC). Th17 cells were evaluated by flow cytometry and the expression of miR-326, miR-155, RORC2 and FOXP3 by qRT-PCR. We also analyzed cytokines from the supernatants of the ATMC culture and measured the FOXP3 methylation percentage by bisulfite conversion by PCR. According to the results, the frequency of Th17 cells and RORC2 expression was higher in individuals with obesity and associated with miR-326 expression. The ATMC from this group secreted a proinflammatory cytokine profile by in vitro assay. In contrast, lower levels of mRNA FOXP3 expression was detected in ATMC from individuals with obesity that correlated with methylation percentage of FOXP3 gene but no association with miR-155 was detected. Our results suggested that miR-326 participates in the polarization towards Th17 promoting the inflammatory state in the obesity-induced adipose tissue.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31136754</pmid><doi>10.1016/j.imlet.2019.05.010</doi><tpages>8</tpages></addata></record> |
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| subjects | Adipose tissue Adipose Tissue - immunology Adult Cell Differentiation Cells, Cultured Female Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism FOXP3 methylation Gene Expression Regulation Humans Inflammation Lymphocyte Activation Male MicroRNAs - genetics Middle Aged miR-155 miR-326 Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism Obesity Obesity - genetics Obesity - immunology T-Lymphocytes, Regulatory - immunology Th17 cells Th17 Cells - immunology Transcription factors Young Adult |
| title | Increased levels of adipose tissue-resident Th17 cells in obesity associated with miR-326 |
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