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Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers  Christopher.

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Presentation on theme: "Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers  Christopher."— Presentation transcript:

1 Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers  Christopher F. Rider, PhD, Masatsugu Yamamoto, MD, Oliver P. Günther, PhD, Jeremy A. Hirota, PhD, Amrit Singh, BS, Scott J. Tebbutt, PhD, Chris Carlsten, MD, MPH  Journal of Allergy and Clinical Immunology  Volume 138, Issue 6, Pages (December 2016) DOI: /j.jaci Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 A, Outline of study design. ∗Order randomized. B, Details of the testing and data analysis performed. brush, Epithelial cell brushings; LLL, left lower lobe; RLL, right lower lobe; RML, right middle lobe. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 miRNA and gene expression were measured with NanoString nCounter Human miRNA v2 (A) and Human Immunology v1 (B) assays, respectively, in total RNA extracted from bronchial brushings. Effects of the indicated conditions were evaluated using robust linear models and Venn diagrams constructed showing miRNAs and mRNAs with q values of ≤0.05. Stars indicate genes whose expression was increased and decreased by different conditions. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Mixed models were used to evaluate the effects of allergen or DE exposure on brushing miRNA (A) and mRNA (B) expression. The 20 miRNAs and mRNAs with the smallest uncorrected P values and q values for allergen exposure were plotted (top panels). Values for the same miRNAs and mRNAs following DE exposure are plotted in the bottom panels. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Bar (mean) and whisker (SD) plots showing the effects of conditions on the expression of the 5 miRNAs and mRNAs with the smallest uncorrected P values for allergen were generated. Gray circles indicate individual participant values. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Mixed effects models demonstrated the effects of allergen or DE exposure on brushing miRNA (A) and mRNA (B) expression. The 20 miRNAs and mRNAs with the smallest uncorrected P values and q values for DE exposure were plotted (top panels). Values for the same miRNAs and mRNAs following allergen exposure were also plotted (bottom panels). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 The miRTarBase database was consulted for miRNAs targeting CDKN1C and those modulated by allergen treatment grouped, with shades of blue indicating the strength of experimental evidence. qPCR, Quantitative PCR; qRT-PCR, quantitative RT-PCR. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig 7 A, Correlations between the 20 miRNAs and mRNAs with the lowest P values following allergen exposure were analyzed by PLS regression and the first 2 components plotted as a heatmap. Blue depicts negative correlation, whereas red indicates positive correlation. B, Network diagrams were constructed showing elements with a correlation of ≥0.7 between variables. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig 8 A, Correlations between the 20 mRNAs and 13 inflammatory mediators with the lowest P values following allergen exposure were analyzed by PLS regression and the first 2 components plotted as a heatmap. Blue depicts negative correlation, whereas red indicates positive correlation. B, Network diagrams were constructed showing elements with a correlation of ≥0.7 between variables. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions


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