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Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood  Anna Lluis, PhD, Martin.

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Presentation on theme: "Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood  Anna Lluis, PhD, Martin."— Presentation transcript:

1 Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood  Anna Lluis, PhD, Martin Depner, PhD, Beatrice Gaugler, PhD, Philippe Saas, PhD, Vera Isabel Casaca, MSc, Diana Raedler, Sven Michel, MSc, Jorg Tost, PhD, Jing Liu, MD, Jon Genuneit, MD, Petra Pfefferle, PhD, Marjut Roponen, PhD, Juliane Weber, MD, Charlotte Braun-Fahrländer, MD, Josef Riedler, MD, Roger Lauener, MD, Dominique Angèle Vuitton, PhD, Jean-Charles Dalphin, MD, PhD, Juha Pekkanen, MD, Erika von Mutius, MD, MSc, Bianca Schaub, MD A. Hyvärinen, A. Karvonen, M.R. Hirvonen, P. Tiittanen, S. Remes, V. Kaulek, M.L. Dalphin, M. Ege M, G. Büchele, S. Bitter, G. Loss, C. Roduit, R. Frei, H. Renz, M. Kabesch, G. Doekes Anna Lluis, PhD, Martin Depner, PhD, Beatrice Gaugler, PhD, Philippe Saas, PhD, Vera Isabel Casaca, MSc, Diana Raedler, Sven Michel, MSc, Jorg Tost, PhD, Jing Liu, MD, Jon Genuneit, MD, Petra Pfefferle, PhD, Marjut Roponen, PhD, Juliane Weber, MD, Charlotte Braun- Fahrländer, MD, Josef Riedler, MD, Roger Lauener, MD, Dominique Angèle Vuitton, PhD, Jean-Charles Dalphin, MD, PhD, Juha Pekkanen, MD, Erika von Mutius, MD, MSc, Bianca Schaub, MD A. Hyvärinen, A. Karvonen, M.R. Hirvonen, P. Tiittanen, S. Remes, V. Kaulek, M.L. Dalphin, M. Ege M, G. Büchele, S. Bitter, G. Loss, C. Roduit, R. Frei, H. Renz, M. Kabesch, G. Doekes  Journal of Allergy and Clinical Immunology  Volume 133, Issue 2, Pages e10 (February 2014) DOI: /j.jaci Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Study design for assessment of Treg cells.
Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Distribution of CD4+ T cells, activated T cells, and Treg cells relative to lymphocytes (as a percentage). Intracellular expression of CD4+, CD4+CD25+, and upper 20% CD4+CD25+, FOXP3+ cells in unstimulated, PI-stimulated, and LPS-stimulated cells (n = 298, Germany and France). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Mediation of the farm milk effect on asthma (doctor's diagnosis at age 4 years, n = 18) by LPS-stimulated Treg cells and activated T cells. The total effect of farm milk on asthma at age 4 years is divided into a direct and an indirect path (estimates and P values of each effect are indicated separately). Upper 20% CD4+CD25+, FOXP3+ (A) versus CD4+CD25+ (B) cells are shown as a possible indirect link between farm milk exposure and asthma, with a more pronounced effect through upper 20% CD4+CD25+, FOXP3+ cells (β = −0.108, P = .079). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig E1 Gating strategies for flow cytometry. A, Assessing Treg cell numbers by means of intracellular staining (upper 20% CD4+CD25+, FOXP3+). B, Assessing Treg cell numbers by means of surface staining (CD4+CD25highCD127−/low cells). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig E2 Distribution of children age 4 years stratified by farm and farm milk consumption and stable contact (A) and stay in a stable and farm milk consumption (B). There are children who consume farm milk and do not have stable contact (n = 12 in reference children) and children with stable contact who do not drink farm milk (n = 19 in reference children). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig E3 Distribution of CD4+, activated T cells, and Treg cells relative to lymphocytes (as a percentage): surface expression of CD4+, CD4+CD25+, and CD4+CD25highCD127low/− cells (n = 157, Germany). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig E4 FOXP3 demethylation (CpGs 1-8 and median of all CpGs) in the TSDR region proximal to the promoter. Demethylation was detectable in CpGs 4 to 8 and was generally higher in children with farm milk exposure compared with those with no farm milk exposure (n = 43 German children, median ± interquartile range). Journal of Allergy and Clinical Immunology  , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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