Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis
Background Development of alcoholic hepatitis (AH) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T cells (Tregs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in...
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| Veröffentlicht in: | Alcoholism, clinical and experimental research clinical and experimental research, 2013-08, Vol.37 (8), p.1361-1369 |
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| container_title | Alcoholism, clinical and experimental research |
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| creator | Almeida, Julia Polvorosa, Maria Angeles Gonzalez-Quintela, Arturo Marcos, Miguel Pastor, Isabel Hernandez Cerceño, Maria Luisa Orfao, Alberto Laso, Francisco-Javier |
| description | Background
Development of alcoholic hepatitis (AH) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T cells (Tregs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of Tregs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood (PB) Tregs and Treg subsets in AH and its relationship with the production of inflammatory cytokines by PB monocytes and dendritic cells (DCs).
Methods
PB samples from 25 male patients with AH were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD) and 17 male healthy donors were also studied, as controls. The distribution of CD4+CD25hiCD127−/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory Tregs) was analyzed by flow cytometry. Spontaneous and in vitro‐stimulated production of inflammatory cytokines by PB monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level.
Results
Patients with AH showed decreased (p 0.05) distribution of PB CD4+CD25hiCD127−/lo Tregs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte‐derived DCs and monocytes from AH (and AWLD) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p |
| doi_str_mv | 10.1111/acer.12095 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1430862588</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3028922411</sourcerecordid><originalsourceid>FETCH-LOGICAL-i3525-7b4ab9384883ea4ec036d069dec354a31e7848f63e449bbd357e649d52de8d893</originalsourceid><addsrcrecordid>eNqFkU1vEzEQhi0EoqFw4QcgS1yQqm1tjz92j2HTD6S2VKGIE7K8u1Pi4mSDvas2_75OU3rgwlw80vu8o_G8hLzn7JDnOnItxkMuWKVekAlXwAomjHlJJoxLVWjGyj3yJqVbxpgstX5N9gQoxXQFE_Jzhm1El7CjVxj9eoHRBfo59H1H65k8OKpnQh3QOf4agxv6uKHXtMYQEvUreuUGj6sh0Ts_LOg0tP2iD76lZ7jOyuDTW_LqxoWE757effL95Pi6PivOv55-qafnhQclVGEa6ZoKSlmWgE5iy0B3eb8OW1DSAUeTtRsNKGXVNB0og1pWnRIdll1ZwT75tJu7jv2fEdNglz61eU23wn5MlktgpRYqz_8_yo0CbkBn9OM_6G0_xlX-yJYSyuQrQ6Y-PFFjs8TOrqNfurixf2-cAb4D7nzAzbPOmd2mZ7fp2cf07LQ-nj922VPsPD4NeP_scfG31QaMsj8uT-3FibiU7GJuv8ED-vWYLw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1412572773</pqid></control><display><type>article</type><title>Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><source>Wiley Online Library Core Title</source><creator>Almeida, Julia ; Polvorosa, Maria Angeles ; Gonzalez-Quintela, Arturo ; Marcos, Miguel ; Pastor, Isabel ; Hernandez Cerceño, Maria Luisa ; Orfao, Alberto ; Laso, Francisco-Javier</creator><creatorcontrib>Almeida, Julia ; Polvorosa, Maria Angeles ; Gonzalez-Quintela, Arturo ; Marcos, Miguel ; Pastor, Isabel ; Hernandez Cerceño, Maria Luisa ; Orfao, Alberto ; Laso, Francisco-Javier</creatorcontrib><description>Background
Development of alcoholic hepatitis (AH) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T cells (Tregs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of Tregs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood (PB) Tregs and Treg subsets in AH and its relationship with the production of inflammatory cytokines by PB monocytes and dendritic cells (DCs).
Methods
PB samples from 25 male patients with AH were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD) and 17 male healthy donors were also studied, as controls. The distribution of CD4+CD25hiCD127−/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory Tregs) was analyzed by flow cytometry. Spontaneous and in vitro‐stimulated production of inflammatory cytokines by PB monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level.
Results
Patients with AH showed decreased (p < 0.05) numbers of PB CD4+CD25hiCD127−/lo Tregs at the expense of all maturation‐associated subsets, while AWLD and healthy subjects showed a similar (p > 0.05) distribution of PB CD4+CD25hiCD127−/lo Tregs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte‐derived DCs and monocytes from AH (and AWLD) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p < 0.05) in AH versus the 2 control groups.
Conclusions
PB CD4+CD25hiCD127−/lo Tregs are significantly decreased in patients with AH when compared to both healthy and AWLD; this may contribute to explain the more pronounced activation of the innate immune response observed in AH, as reflected by an increased secretion of inflammatory cytokines by PB DCs and monocytes, and could facilitate the development of liver disease.</description><identifier>ISSN: 0145-6008</identifier><identifier>EISSN: 1530-0277</identifier><identifier>DOI: 10.1111/acer.12095</identifier><identifier>PMID: 23550693</identifier><identifier>CODEN: ACRSDM</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Acute-Phase Proteins ; Adult ; Alcoholic Hepatitis ; Carrier Proteins - blood ; Case-Control Studies ; CD4+ CD25hi CD127−/lo Tregs ; Cell Proliferation ; Chronic Alcoholism ; Cytokines - metabolism ; Dendritic Cells - metabolism ; Hepatitis, Alcoholic - immunology ; Hepatitis, Alcoholic - pathology ; Humans ; Inflammatory Cytokines ; Lymphocyte Depletion ; Male ; Membrane Glycoproteins - blood ; Middle Aged ; Monocytes - metabolism ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - pathology</subject><ispartof>Alcoholism, clinical and experimental research, 2013-08, Vol.37 (8), p.1361-1369</ispartof><rights>Copyright © 2013 by the Research Society on Alcoholism</rights><rights>Copyright © 2013 by the Research Society on Alcoholism.</rights><rights>2013 Research Society on Alcoholism</rights><lds50>peer_reviewed</lds50><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/10.1111%2Facer.12095$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Facer.12095$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23550693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Almeida, Julia</creatorcontrib><creatorcontrib>Polvorosa, Maria Angeles</creatorcontrib><creatorcontrib>Gonzalez-Quintela, Arturo</creatorcontrib><creatorcontrib>Marcos, Miguel</creatorcontrib><creatorcontrib>Pastor, Isabel</creatorcontrib><creatorcontrib>Hernandez Cerceño, Maria Luisa</creatorcontrib><creatorcontrib>Orfao, Alberto</creatorcontrib><creatorcontrib>Laso, Francisco-Javier</creatorcontrib><title>Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis</title><title>Alcoholism, clinical and experimental research</title><addtitle>Alcohol Clin Exp Res</addtitle><description>Background
Development of alcoholic hepatitis (AH) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T cells (Tregs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of Tregs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood (PB) Tregs and Treg subsets in AH and its relationship with the production of inflammatory cytokines by PB monocytes and dendritic cells (DCs).
Methods
PB samples from 25 male patients with AH were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD) and 17 male healthy donors were also studied, as controls. The distribution of CD4+CD25hiCD127−/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory Tregs) was analyzed by flow cytometry. Spontaneous and in vitro‐stimulated production of inflammatory cytokines by PB monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level.
Results
Patients with AH showed decreased (p < 0.05) numbers of PB CD4+CD25hiCD127−/lo Tregs at the expense of all maturation‐associated subsets, while AWLD and healthy subjects showed a similar (p > 0.05) distribution of PB CD4+CD25hiCD127−/lo Tregs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte‐derived DCs and monocytes from AH (and AWLD) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p < 0.05) in AH versus the 2 control groups.
Conclusions
PB CD4+CD25hiCD127−/lo Tregs are significantly decreased in patients with AH when compared to both healthy and AWLD; this may contribute to explain the more pronounced activation of the innate immune response observed in AH, as reflected by an increased secretion of inflammatory cytokines by PB DCs and monocytes, and could facilitate the development of liver disease.</description><subject>Acute-Phase Proteins</subject><subject>Adult</subject><subject>Alcoholic Hepatitis</subject><subject>Carrier Proteins - blood</subject><subject>Case-Control Studies</subject><subject>CD4+ CD25hi CD127−/lo Tregs</subject><subject>Cell Proliferation</subject><subject>Chronic Alcoholism</subject><subject>Cytokines - metabolism</subject><subject>Dendritic Cells - metabolism</subject><subject>Hepatitis, Alcoholic - immunology</subject><subject>Hepatitis, Alcoholic - pathology</subject><subject>Humans</subject><subject>Inflammatory Cytokines</subject><subject>Lymphocyte Depletion</subject><subject>Male</subject><subject>Membrane Glycoproteins - blood</subject><subject>Middle Aged</subject><subject>Monocytes - metabolism</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - pathology</subject><issn>0145-6008</issn><issn>1530-0277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EoqFw4QcgS1yQqm1tjz92j2HTD6S2VKGIE7K8u1Pi4mSDvas2_75OU3rgwlw80vu8o_G8hLzn7JDnOnItxkMuWKVekAlXwAomjHlJJoxLVWjGyj3yJqVbxpgstX5N9gQoxXQFE_Jzhm1El7CjVxj9eoHRBfo59H1H65k8OKpnQh3QOf4agxv6uKHXtMYQEvUreuUGj6sh0Ts_LOg0tP2iD76lZ7jOyuDTW_LqxoWE757effL95Pi6PivOv55-qafnhQclVGEa6ZoKSlmWgE5iy0B3eb8OW1DSAUeTtRsNKGXVNB0og1pWnRIdll1ZwT75tJu7jv2fEdNglz61eU23wn5MlktgpRYqz_8_yo0CbkBn9OM_6G0_xlX-yJYSyuQrQ6Y-PFFjs8TOrqNfurixf2-cAb4D7nzAzbPOmd2mZ7fp2cf07LQ-nj922VPsPD4NeP_scfG31QaMsj8uT-3FibiU7GJuv8ED-vWYLw</recordid><startdate>201308</startdate><enddate>201308</enddate><creator>Almeida, Julia</creator><creator>Polvorosa, Maria Angeles</creator><creator>Gonzalez-Quintela, Arturo</creator><creator>Marcos, Miguel</creator><creator>Pastor, Isabel</creator><creator>Hernandez Cerceño, Maria Luisa</creator><creator>Orfao, Alberto</creator><creator>Laso, Francisco-Javier</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>K7.</scope><scope>K9.</scope><scope>7X8</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>201308</creationdate><title>Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis</title><author>Almeida, Julia ; Polvorosa, Maria Angeles ; Gonzalez-Quintela, Arturo ; Marcos, Miguel ; Pastor, Isabel ; Hernandez Cerceño, Maria Luisa ; Orfao, Alberto ; Laso, Francisco-Javier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3525-7b4ab9384883ea4ec036d069dec354a31e7848f63e449bbd357e649d52de8d893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Acute-Phase Proteins</topic><topic>Adult</topic><topic>Alcoholic Hepatitis</topic><topic>Carrier Proteins - blood</topic><topic>Case-Control Studies</topic><topic>CD4+ CD25hi CD127−/lo Tregs</topic><topic>Cell Proliferation</topic><topic>Chronic Alcoholism</topic><topic>Cytokines - metabolism</topic><topic>Dendritic Cells - metabolism</topic><topic>Hepatitis, Alcoholic - immunology</topic><topic>Hepatitis, Alcoholic - pathology</topic><topic>Humans</topic><topic>Inflammatory Cytokines</topic><topic>Lymphocyte Depletion</topic><topic>Male</topic><topic>Membrane Glycoproteins - blood</topic><topic>Middle Aged</topic><topic>Monocytes - metabolism</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Almeida, Julia</creatorcontrib><creatorcontrib>Polvorosa, Maria Angeles</creatorcontrib><creatorcontrib>Gonzalez-Quintela, Arturo</creatorcontrib><creatorcontrib>Marcos, Miguel</creatorcontrib><creatorcontrib>Pastor, Isabel</creatorcontrib><creatorcontrib>Hernandez Cerceño, Maria Luisa</creatorcontrib><creatorcontrib>Orfao, Alberto</creatorcontrib><creatorcontrib>Laso, Francisco-Javier</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Alcoholism, clinical and experimental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Almeida, Julia</au><au>Polvorosa, Maria Angeles</au><au>Gonzalez-Quintela, Arturo</au><au>Marcos, Miguel</au><au>Pastor, Isabel</au><au>Hernandez Cerceño, Maria Luisa</au><au>Orfao, Alberto</au><au>Laso, Francisco-Javier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis</atitle><jtitle>Alcoholism, clinical and experimental research</jtitle><addtitle>Alcohol Clin Exp Res</addtitle><date>2013-08</date><risdate>2013</risdate><volume>37</volume><issue>8</issue><spage>1361</spage><epage>1369</epage><pages>1361-1369</pages><issn>0145-6008</issn><eissn>1530-0277</eissn><coden>ACRSDM</coden><abstract>Background
Development of alcoholic hepatitis (AH) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T cells (Tregs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of Tregs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood (PB) Tregs and Treg subsets in AH and its relationship with the production of inflammatory cytokines by PB monocytes and dendritic cells (DCs).
Methods
PB samples from 25 male patients with AH were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD) and 17 male healthy donors were also studied, as controls. The distribution of CD4+CD25hiCD127−/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory Tregs) was analyzed by flow cytometry. Spontaneous and in vitro‐stimulated production of inflammatory cytokines by PB monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level.
Results
Patients with AH showed decreased (p < 0.05) numbers of PB CD4+CD25hiCD127−/lo Tregs at the expense of all maturation‐associated subsets, while AWLD and healthy subjects showed a similar (p > 0.05) distribution of PB CD4+CD25hiCD127−/lo Tregs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte‐derived DCs and monocytes from AH (and AWLD) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p < 0.05) in AH versus the 2 control groups.
Conclusions
PB CD4+CD25hiCD127−/lo Tregs are significantly decreased in patients with AH when compared to both healthy and AWLD; this may contribute to explain the more pronounced activation of the innate immune response observed in AH, as reflected by an increased secretion of inflammatory cytokines by PB DCs and monocytes, and could facilitate the development of liver disease.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23550693</pmid><doi>10.1111/acer.12095</doi><tpages>9</tpages></addata></record> |
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| ispartof | Alcoholism, clinical and experimental research, 2013-08, Vol.37 (8), p.1361-1369 |
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| subjects | Acute-Phase Proteins Adult Alcoholic Hepatitis Carrier Proteins - blood Case-Control Studies CD4+ CD25hi CD127−/lo Tregs Cell Proliferation Chronic Alcoholism Cytokines - metabolism Dendritic Cells - metabolism Hepatitis, Alcoholic - immunology Hepatitis, Alcoholic - pathology Humans Inflammatory Cytokines Lymphocyte Depletion Male Membrane Glycoproteins - blood Middle Aged Monocytes - metabolism T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - pathology |
| title | Decreased Peripheral Blood CD4+/CD25+ Regulatory T Cells in Patients with Alcoholic Hepatitis |
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