Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood
Background European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T...
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| creator | Lluis, Anna, PhD Depner, Martin, PhD Gaugler, Beatrice, PhD Saas, Philippe, PhD Casaca, Vera Isabel, MSc Raedler, Diana Michel, Sven, MSc Tost, Jorg, PhD Liu, Jing, MD Genuneit, Jon, MD Pfefferle, Petra, PhD Roponen, Marjut, PhD Weber, Juliane, MD Braun-Fahrländer, Charlotte, MD Riedler, Josef, MD Lauener, Roger, MD Vuitton, Dominique Angèle, PhD Dalphin, Jean-Charles, MD, PhD Pekkanen, Juha, MD von Mutius, Erika, MD, MSc Schaub, Bianca, MD |
| description | Background European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+ CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+ CD25+ , FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases. |
| doi_str_mv | 10.1016/j.jaci.2013.06.034 |
| format | Article |
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Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+ CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+ CD25+ , FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2013.06.034</identifier><identifier>PMID: 23993223</identifier><identifier>CODEN: JACIBY</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Agriculture ; Allergies ; Allergy and Immunology ; Animals ; Asthma ; Asthma - diagnosis ; Asthma - immunology ; atopic sensitization ; Biological and medical sciences ; CD4 Lymphocyte Count ; Child, Preschool ; Chronic obstructive pulmonary disease, asthma ; DNA Methylation ; Ecology, environment ; Europe ; farming ; Female ; Forkhead Transcription Factors ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - immunology ; FOXP3 demethylation ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Health ; Humans ; Hypersensitivity, Immediate ; Hypersensitivity, Immediate - diagnosis ; Hypersensitivity, Immediate - immunology ; Immunoglobulin E ; Immunoglobulin E - blood ; Immunopathology ; Infant ; innate ; Life Sciences ; Male ; Medical sciences ; Milk ; peripheral blood mononuclear cells ; Pneumology ; Pregnancy ; Prospective Studies ; regulatory T cells ; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis ; Studies ; T-Lymphocytes, Regulatory ; T-Lymphocytes, Regulatory - cytology ; T-Lymphocytes, Regulatory - immunology ; Womens health</subject><ispartof>Journal of allergy and clinical immunology, 2014-02, Vol.133 (2), p.551-559.e10</ispartof><rights>American Academy of Allergy, Asthma & Immunology</rights><rights>2013 American Academy of Allergy, Asthma & Immunology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 2014</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c580t-3e849dbdef7dcbac9fdb79f2b3f248129814ad4ad4bb20334857b528e4e3fbf23</citedby><cites>FETCH-LOGICAL-c580t-3e849dbdef7dcbac9fdb79f2b3f248129814ad4ad4bb20334857b528e4e3fbf23</cites><orcidid>0000-0001-5764-1528 ; 0000-0002-8290-3494</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0091674913010506$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28244823$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23993223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01063986$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Lluis, Anna, PhD</creatorcontrib><creatorcontrib>Depner, Martin, PhD</creatorcontrib><creatorcontrib>Gaugler, Beatrice, PhD</creatorcontrib><creatorcontrib>Saas, Philippe, PhD</creatorcontrib><creatorcontrib>Casaca, Vera Isabel, MSc</creatorcontrib><creatorcontrib>Raedler, Diana</creatorcontrib><creatorcontrib>Michel, Sven, MSc</creatorcontrib><creatorcontrib>Tost, Jorg, PhD</creatorcontrib><creatorcontrib>Liu, Jing, MD</creatorcontrib><creatorcontrib>Genuneit, Jon, MD</creatorcontrib><creatorcontrib>Pfefferle, Petra, PhD</creatorcontrib><creatorcontrib>Roponen, Marjut, PhD</creatorcontrib><creatorcontrib>Weber, Juliane, MD</creatorcontrib><creatorcontrib>Braun-Fahrländer, Charlotte, MD</creatorcontrib><creatorcontrib>Riedler, Josef, MD</creatorcontrib><creatorcontrib>Lauener, Roger, MD</creatorcontrib><creatorcontrib>Vuitton, Dominique Angèle, PhD</creatorcontrib><creatorcontrib>Dalphin, Jean-Charles, MD, PhD</creatorcontrib><creatorcontrib>Pekkanen, Juha, MD</creatorcontrib><creatorcontrib>von Mutius, Erika, MD, MSc</creatorcontrib><creatorcontrib>Schaub, Bianca, MD</creatorcontrib><creatorcontrib>Protection Against Allergy: Study in Rural Environments Study Group</creatorcontrib><title>Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Background European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+ CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+ CD25+ , FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.</description><subject>Agriculture</subject><subject>Allergies</subject><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Asthma</subject><subject>Asthma - diagnosis</subject><subject>Asthma - immunology</subject><subject>atopic sensitization</subject><subject>Biological and medical sciences</subject><subject>CD4 Lymphocyte Count</subject><subject>Child, Preschool</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>DNA Methylation</subject><subject>Ecology, environment</subject><subject>Europe</subject><subject>farming</subject><subject>Female</subject><subject>Forkhead Transcription Factors</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - immunology</subject><subject>FOXP3 demethylation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Health</subject><subject>Humans</subject><subject>Hypersensitivity, Immediate</subject><subject>Hypersensitivity, Immediate - diagnosis</subject><subject>Hypersensitivity, Immediate - immunology</subject><subject>Immunoglobulin E</subject><subject>Immunoglobulin E - blood</subject><subject>Immunopathology</subject><subject>Infant</subject><subject>innate</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Milk</subject><subject>peripheral blood mononuclear cells</subject><subject>Pneumology</subject><subject>Pregnancy</subject><subject>Prospective Studies</subject><subject>regulatory T cells</subject><subject>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</subject><subject>Studies</subject><subject>T-Lymphocytes, Regulatory</subject><subject>T-Lymphocytes, Regulatory - cytology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Womens health</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkl1rFDEUhoMotq7-AS8kIIJezJqP-UigCKWoLSx4Yb0OmeSMm-1MsiYzreud_9xMd22hFyIEQpLnnLznvAehl5QsKaH1-81yo41bMkL5ktRLwstH6JgS2RS1YNVjdEyIpEXdlPIIPUtpQ_KZC_kUHTEuJWeMH6PfF95E0AksjvB96vUY4g5fFgb6HvtpaCEmrCNgnVIwTo8ZvHHjGnc6Dnhw_RWGn9uQphnxFvfhBiLOWbbO4AQ-udH90qML_vZZp3E9aOw8NmvX23UI9jl60uk-wYvDvkDfPn28PDsvVl8-X5ydrgpTCTIWHEQpbWuha6xptZGdbRvZsZZ3rBSUSUFLbefVtoxwXoqqaSsmoATetR3jC_Run3ete7WNbtBxp4J26vx0peY7QknNpaivaWbf7tltDD8mSKMaXJpboj2EKSla1YTmJrLmP1Ai6kY0lGf09QN0E6boc9EzVQrGeVa-QGxPmRhSitDdiaVEzb6rjZp9V7PvitQq-56DXh1ST-0A9i7kr9EZeHMAdDK676L2xqV7TrDyVsACnew5yFZcO4gqGQfegHURzKhscP_W8eFBuOmdd_nHK9hBuq9XJaaI-jpP6DyglOfuV7n_fwAzqOCw</recordid><startdate>20140201</startdate><enddate>20140201</enddate><creator>Lluis, Anna, PhD</creator><creator>Depner, Martin, PhD</creator><creator>Gaugler, Beatrice, PhD</creator><creator>Saas, Philippe, PhD</creator><creator>Casaca, Vera Isabel, MSc</creator><creator>Raedler, Diana</creator><creator>Michel, Sven, MSc</creator><creator>Tost, Jorg, PhD</creator><creator>Liu, Jing, MD</creator><creator>Genuneit, Jon, MD</creator><creator>Pfefferle, Petra, PhD</creator><creator>Roponen, Marjut, PhD</creator><creator>Weber, Juliane, MD</creator><creator>Braun-Fahrländer, Charlotte, MD</creator><creator>Riedler, Josef, MD</creator><creator>Lauener, Roger, MD</creator><creator>Vuitton, Dominique Angèle, PhD</creator><creator>Dalphin, Jean-Charles, MD, PhD</creator><creator>Pekkanen, Juha, MD</creator><creator>von Mutius, Erika, MD, MSc</creator><creator>Schaub, Bianca, MD</creator><general>Mosby, Inc</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><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>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-5764-1528</orcidid><orcidid>https://orcid.org/0000-0002-8290-3494</orcidid></search><sort><creationdate>20140201</creationdate><title>Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood</title><author>Lluis, Anna, PhD ; Depner, Martin, PhD ; Gaugler, Beatrice, PhD ; Saas, Philippe, PhD ; Casaca, Vera Isabel, MSc ; Raedler, Diana ; Michel, Sven, MSc ; Tost, Jorg, PhD ; Liu, Jing, MD ; Genuneit, Jon, MD ; Pfefferle, Petra, PhD ; Roponen, Marjut, PhD ; Weber, Juliane, MD ; Braun-Fahrländer, Charlotte, MD ; Riedler, Josef, MD ; Lauener, Roger, MD ; Vuitton, Dominique Angèle, PhD ; Dalphin, Jean-Charles, MD, PhD ; Pekkanen, Juha, MD ; von Mutius, Erika, MD, MSc ; Schaub, Bianca, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c580t-3e849dbdef7dcbac9fdb79f2b3f248129814ad4ad4bb20334857b528e4e3fbf23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Agriculture</topic><topic>Allergies</topic><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Asthma</topic><topic>Asthma - diagnosis</topic><topic>Asthma - immunology</topic><topic>atopic sensitization</topic><topic>Biological and medical sciences</topic><topic>CD4 Lymphocyte Count</topic><topic>Child, Preschool</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>DNA Methylation</topic><topic>Ecology, environment</topic><topic>Europe</topic><topic>farming</topic><topic>Female</topic><topic>Forkhead Transcription Factors</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - immunology</topic><topic>FOXP3 demethylation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Health</topic><topic>Humans</topic><topic>Hypersensitivity, Immediate</topic><topic>Hypersensitivity, Immediate - diagnosis</topic><topic>Hypersensitivity, Immediate - immunology</topic><topic>Immunoglobulin E</topic><topic>Immunoglobulin E - blood</topic><topic>Immunopathology</topic><topic>Infant</topic><topic>innate</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Milk</topic><topic>peripheral blood mononuclear cells</topic><topic>Pneumology</topic><topic>Pregnancy</topic><topic>Prospective Studies</topic><topic>regulatory T cells</topic><topic>Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis</topic><topic>Studies</topic><topic>T-Lymphocytes, Regulatory</topic><topic>T-Lymphocytes, Regulatory - cytology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lluis, Anna, PhD</creatorcontrib><creatorcontrib>Depner, Martin, PhD</creatorcontrib><creatorcontrib>Gaugler, Beatrice, PhD</creatorcontrib><creatorcontrib>Saas, Philippe, PhD</creatorcontrib><creatorcontrib>Casaca, Vera Isabel, MSc</creatorcontrib><creatorcontrib>Raedler, Diana</creatorcontrib><creatorcontrib>Michel, Sven, MSc</creatorcontrib><creatorcontrib>Tost, Jorg, PhD</creatorcontrib><creatorcontrib>Liu, Jing, MD</creatorcontrib><creatorcontrib>Genuneit, Jon, MD</creatorcontrib><creatorcontrib>Pfefferle, Petra, PhD</creatorcontrib><creatorcontrib>Roponen, Marjut, PhD</creatorcontrib><creatorcontrib>Weber, Juliane, MD</creatorcontrib><creatorcontrib>Braun-Fahrländer, Charlotte, MD</creatorcontrib><creatorcontrib>Riedler, Josef, MD</creatorcontrib><creatorcontrib>Lauener, Roger, MD</creatorcontrib><creatorcontrib>Vuitton, Dominique Angèle, PhD</creatorcontrib><creatorcontrib>Dalphin, Jean-Charles, MD, PhD</creatorcontrib><creatorcontrib>Pekkanen, Juha, MD</creatorcontrib><creatorcontrib>von Mutius, Erika, MD, MSc</creatorcontrib><creatorcontrib>Schaub, Bianca, MD</creatorcontrib><creatorcontrib>Protection Against Allergy: Study in Rural Environments Study Group</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lluis, Anna, PhD</au><au>Depner, Martin, PhD</au><au>Gaugler, Beatrice, PhD</au><au>Saas, Philippe, PhD</au><au>Casaca, Vera Isabel, MSc</au><au>Raedler, Diana</au><au>Michel, Sven, MSc</au><au>Tost, Jorg, PhD</au><au>Liu, Jing, MD</au><au>Genuneit, Jon, MD</au><au>Pfefferle, Petra, PhD</au><au>Roponen, Marjut, PhD</au><au>Weber, Juliane, MD</au><au>Braun-Fahrländer, Charlotte, MD</au><au>Riedler, Josef, MD</au><au>Lauener, Roger, MD</au><au>Vuitton, Dominique Angèle, PhD</au><au>Dalphin, Jean-Charles, MD, PhD</au><au>Pekkanen, Juha, MD</au><au>von Mutius, Erika, MD, MSc</au><au>Schaub, Bianca, MD</au><aucorp>Protection Against Allergy: Study in Rural Environments Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>133</volume><issue>2</issue><spage>551</spage><epage>559.e10</epage><pages>551-559.e10</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><coden>JACIBY</coden><abstract>Background European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+ CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+ CD25+ , FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>23993223</pmid><doi>10.1016/j.jaci.2013.06.034</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-5764-1528</orcidid><orcidid>https://orcid.org/0000-0002-8290-3494</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0091-6749 |
| ispartof | Journal of allergy and clinical immunology, 2014-02, Vol.133 (2), p.551-559.e10 |
| issn | 0091-6749 1097-6825 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_01063986v1 |
| source | MEDLINE; Elsevier ScienceDirect Journals; EZB Electronic Journals Library |
| subjects | Agriculture Allergies Allergy and Immunology Animals Asthma Asthma - diagnosis Asthma - immunology atopic sensitization Biological and medical sciences CD4 Lymphocyte Count Child, Preschool Chronic obstructive pulmonary disease, asthma DNA Methylation Ecology, environment Europe farming Female Forkhead Transcription Factors Forkhead Transcription Factors - genetics Forkhead Transcription Factors - immunology FOXP3 demethylation Fundamental and applied biological sciences. Psychology Fundamental immunology Health Humans Hypersensitivity, Immediate Hypersensitivity, Immediate - diagnosis Hypersensitivity, Immediate - immunology Immunoglobulin E Immunoglobulin E - blood Immunopathology Infant innate Life Sciences Male Medical sciences Milk peripheral blood mononuclear cells Pneumology Pregnancy Prospective Studies regulatory T cells Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis Studies T-Lymphocytes, Regulatory T-Lymphocytes, Regulatory - cytology T-Lymphocytes, Regulatory - immunology Womens health |
| title | Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T09%3A50%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Increased%20regulatory%20T-cell%20numbers%20are%20associated%20with%20farm%20milk%20exposure%20and%20lower%20atopic%20sensitization%20and%20asthma%20in%20childhood&rft.jtitle=Journal%20of%20allergy%20and%20clinical%20immunology&rft.au=Lluis,%20Anna,%20PhD&rft.aucorp=Protection%20Against%20Allergy:%20Study%20in%20Rural%20Environments%20Study%20Group&rft.date=2014-02-01&rft.volume=133&rft.issue=2&rft.spage=551&rft.epage=559.e10&rft.pages=551-559.e10&rft.issn=0091-6749&rft.eissn=1097-6825&rft.coden=JACIBY&rft_id=info:doi/10.1016/j.jaci.2013.06.034&rft_dat=%3Cproquest_hal_p%3E3239409951%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1504823320&rft_id=info:pmid/23993223&rft_els_id=1_s2_0_S0091674913010506&rfr_iscdi=true |