Impact of HIV-ART on the restoration of Th17 and Treg cells in blood and female genital mucosa
The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obt...
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creator | Caruso, María Paula Falivene, Juliana Holgado, María Pía Zurita, Diego Hernán Laufer, Natalia Castro, Carina Nico, Ángeles Maeto, Cynthia Salido, Jimena Pérez, Héctor Salomón, Horacio Cahn, Pedro Sued, Omar Fink, Valeria Turk, Gabriela Gherardi, María Magdalena |
description | The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level. |
doi_str_mv | 10.1038/s41598-019-38547-1 |
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To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-38547-1</identifier><identifier>PMID: 30760809</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/21 ; 13/31 ; 631/250/255/2514 ; 631/250/347 ; 631/326/596/2553 ; 82/80 ; Adult ; Anti-Retroviral Agents - pharmacology ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; CCL17 protein ; CCL20 protein ; Chemokine CCL17 - analysis ; Chemokine CCL20 - analysis ; Chemokine CXCL1 - analysis ; Chemokine CXCL5 - analysis ; Chemokines ; Cytokines - analysis ; Female ; Females ; Genital tract ; Genitalia, Female - cytology ; Genitalia, Female - drug effects ; Genitalia, Female - immunology ; Helper cells ; HIV ; HIV Infections - drug therapy ; Human immunodeficiency virus ; Humanities and Social Sciences ; Humans ; Immunoregulation ; Interleukin 21 ; Interleukin-17 - analysis ; Intestine ; Leukocytes (mononuclear) ; Lymphocytes T ; Middle Aged ; Mucosa ; Mucous Membrane - cytology ; Mucous Membrane - immunology ; Mucous Membrane - metabolism ; multidisciplinary ; Peripheral blood ; Science ; Science (multidisciplinary) ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; Th17 Cells - drug effects ; Th17 Cells - immunology</subject><ispartof>Scientific reports, 2019-02, Vol.9 (1), p.1978, Article 1978</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-8b67508a259035c87eca87098618aa6b94e9881447ee5f18b9f7aabdc4f619053</citedby><cites>FETCH-LOGICAL-c474t-8b67508a259035c87eca87098618aa6b94e9881447ee5f18b9f7aabdc4f619053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374372/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374372/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30760809$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caruso, María Paula</creatorcontrib><creatorcontrib>Falivene, Juliana</creatorcontrib><creatorcontrib>Holgado, María Pía</creatorcontrib><creatorcontrib>Zurita, Diego Hernán</creatorcontrib><creatorcontrib>Laufer, Natalia</creatorcontrib><creatorcontrib>Castro, Carina</creatorcontrib><creatorcontrib>Nico, Ángeles</creatorcontrib><creatorcontrib>Maeto, Cynthia</creatorcontrib><creatorcontrib>Salido, Jimena</creatorcontrib><creatorcontrib>Pérez, Héctor</creatorcontrib><creatorcontrib>Salomón, Horacio</creatorcontrib><creatorcontrib>Cahn, Pedro</creatorcontrib><creatorcontrib>Sued, Omar</creatorcontrib><creatorcontrib>Fink, Valeria</creatorcontrib><creatorcontrib>Turk, Gabriela</creatorcontrib><creatorcontrib>Gherardi, María Magdalena</creatorcontrib><title>Impact of HIV-ART on the restoration of Th17 and Treg cells in blood and female genital mucosa</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level.</description><subject>13</subject><subject>13/21</subject><subject>13/31</subject><subject>631/250/255/2514</subject><subject>631/250/347</subject><subject>631/326/596/2553</subject><subject>82/80</subject><subject>Adult</subject><subject>Anti-Retroviral Agents - pharmacology</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>CCL17 protein</subject><subject>CCL20 protein</subject><subject>Chemokine CCL17 - analysis</subject><subject>Chemokine CCL20 - analysis</subject><subject>Chemokine CXCL1 - analysis</subject><subject>Chemokine CXCL5 - analysis</subject><subject>Chemokines</subject><subject>Cytokines - analysis</subject><subject>Female</subject><subject>Females</subject><subject>Genital tract</subject><subject>Genitalia, Female - cytology</subject><subject>Genitalia, Female - drug effects</subject><subject>Genitalia, Female - immunology</subject><subject>Helper cells</subject><subject>HIV</subject><subject>HIV Infections - drug therapy</subject><subject>Human immunodeficiency virus</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunoregulation</subject><subject>Interleukin 21</subject><subject>Interleukin-17 - analysis</subject><subject>Intestine</subject><subject>Leukocytes (mononuclear)</subject><subject>Lymphocytes T</subject><subject>Middle Aged</subject><subject>Mucosa</subject><subject>Mucous Membrane - cytology</subject><subject>Mucous Membrane - immunology</subject><subject>Mucous Membrane - metabolism</subject><subject>multidisciplinary</subject><subject>Peripheral blood</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>T-Lymphocytes, Regulatory - drug effects</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Th17 Cells - drug effects</subject><subject>Th17 Cells - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caruso, María Paula</au><au>Falivene, Juliana</au><au>Holgado, María Pía</au><au>Zurita, Diego Hernán</au><au>Laufer, Natalia</au><au>Castro, Carina</au><au>Nico, Ángeles</au><au>Maeto, Cynthia</au><au>Salido, Jimena</au><au>Pérez, Héctor</au><au>Salomón, Horacio</au><au>Cahn, Pedro</au><au>Sued, Omar</au><au>Fink, Valeria</au><au>Turk, Gabriela</au><au>Gherardi, María Magdalena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of HIV-ART on the restoration of Th17 and Treg cells in blood and female genital mucosa</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-02-13</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>1978</spage><pages>1978-</pages><artnum>1978</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The aim of this study was to evaluate the effectiveness of antiretroviral treatment (ART) on the proportion and functions of Th17 and Treg cells in peripheral blood and female genital tract (FGT) respectively. To this aim, samples from 41 HIV-neg, 33 HIV+ ART-naïve and 32 HIV+ ART+ subjects were obtained. In peripheral blood, altered Th17 and Th17/Treg proportions were normalized in HIV+ ART+, but certain abnormal Treg and activated T-cell proportions were still observed. In FGT, abnormal patterns of secretion for Th17-related cytokines were observed in cervical mononuclear cells (CMCs) from HIV+ women, even in those from HIV+ ART+, compared to the HIV-neg group. Moreover, these altered patterns of secretion were associated with diminished levels of CXCL5 and CXCL1 chemokines and with an immunoregulatory skew in the CCL17/CCL20 ratio in ectocervix samples of these women. Finally, ART did not restore proportions of Th17-precursor cells with gut-homing potential in PBMCs, and positive correlations between these cells and the levels of IL-17F and IL-21 production by CMCs may suggest that a better homing of these cells to the intestine could also imply a better restoration of these cells in the female genital tract. These results indicate that antiretroviral treatment did not restore Th17-related immune functions completely at the female mucosal level.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30760809</pmid><doi>10.1038/s41598-019-38547-1</doi><oa>free_for_read</oa></addata></record> |
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subjects | 13 13/21 13/31 631/250/255/2514 631/250/347 631/326/596/2553 82/80 Adult Anti-Retroviral Agents - pharmacology Antiretroviral agents Antiretroviral drugs Antiretroviral therapy CCL17 protein CCL20 protein Chemokine CCL17 - analysis Chemokine CCL20 - analysis Chemokine CXCL1 - analysis Chemokine CXCL5 - analysis Chemokines Cytokines - analysis Female Females Genital tract Genitalia, Female - cytology Genitalia, Female - drug effects Genitalia, Female - immunology Helper cells HIV HIV Infections - drug therapy Human immunodeficiency virus Humanities and Social Sciences Humans Immunoregulation Interleukin 21 Interleukin-17 - analysis Intestine Leukocytes (mononuclear) Lymphocytes T Middle Aged Mucosa Mucous Membrane - cytology Mucous Membrane - immunology Mucous Membrane - metabolism multidisciplinary Peripheral blood Science Science (multidisciplinary) T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Th17 Cells - drug effects Th17 Cells - immunology |
title | Impact of HIV-ART on the restoration of Th17 and Treg cells in blood and female genital mucosa |
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