Janina Dose, PhD, Anke Schloesser, PhD, Guillermo G

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Presentation transcript:

On a Western diet, APOE ɛ4 is associated with low innate immune sensing, but not APOE ɛ3 Janina Dose, PhD, Anke Schloesser, PhD, Guillermo G. Torres, MSc, Geetha Venkatesh, PhD, Robert Häsler, PhD, Friederike Flachsbart, PhD, Wolfgang Lieb, MD, Almut Nebel, PhD, Gerald Rimbach, PhD, Patricia Huebbe, PhD Journal of Allergy and Clinical Immunology Volume 142, Issue 4, Pages 1346-1349.e9 (October 2018) DOI: 10.1016/j.jaci.2018.05.033 Copyright © 2018 The Authors Terms and Conditions

Fig 1 Lower expression of TLRs in blood of APOE ɛ4/ɛ3 heterozygous vs APOE ɛ3/ɛ3 homozygous individuals. Box plots; respective P values given above each plot. Multilinear regression; age- and gender-corrected data. Significant and borderline significant P values highlighted in bold. X-axis represents APOE genotypes, Y-axis the quantile-normalized log2 FPKM. FPKM, Fragments per kilobase of exon per million fragments mapped. Journal of Allergy and Clinical Immunology 2018 142, 1346-1349.e9DOI: (10.1016/j.jaci.2018.05.033) Copyright © 2018 The Authors Terms and Conditions

Fig 2 Lower levels of inflammatory markers in APOE ɛ4/ɛ4 versus APOE ɛ3/ɛ3 TR mice fed a WD. A, Final mean liver weights (n = 5-6). B-D, Expression of inflammatory markers in liver and plasma; hepatic Lbp, Cd14, Tlr4, Tnf-α, Il6, and Cd36 gene expression (Fig 2, B), and plasma levels of LBP (Fig 2, C) and CD14 (Fig 2, D) (n = 4-10). E, IAP activity levels in feces (n = 6). F, Hepatic ALP activity (n = 4-10). mRNA relative quantities of target genes in samples determined from known relative quantities of standard RNA. Values for the WD groups pooled from 2 mouse studies after normalization. ELISA measurements performed in duplicate for more than half of the samples in each group. IAP and ALP activity levels measured in duplicate. All values are means + SEM; significant and borderline significant P values given above the respective bars. Journal of Allergy and Clinical Immunology 2018 142, 1346-1349.e9DOI: (10.1016/j.jaci.2018.05.033) Copyright © 2018 The Authors Terms and Conditions

Fig E1 Activation of IκBα in APOE ɛ4/ɛ4 vs APOE ɛ3/ɛ3 mice subjected to different dietary regimens. Protein levels were determined by Western blotting. Blots and corresponding loading controls are shown (A). B and C, Densitometric analysis; all bands are normalized to the total protein content per lane. IκBα activation is shown as the ratio between pIκBα and its unphosphorylated form IκBα. All values are means + SEM (n = 5-6). P values are shown above the respective bars. Journal of Allergy and Clinical Immunology 2018 142, 1346-1349.e9DOI: (10.1016/j.jaci.2018.05.033) Copyright © 2018 The Authors Terms and Conditions

Fig E2 Alkaline phosphatase activity in feces and liver of APOE TR mice subjected to different dietary regimens. A, IAP activity in feces. B, Hepatic ALP activity. C, Correlation of hepatic ALP activity with body weight. A-C, The values for the WD groups were pooled from 2 mouse studies. Values are means + SEM (n = 4-10); linear regression, gender-corrected data. P values are given above the respective bars (Fig E2, A and B) and next to the graph (Fig E2, C), respectively. Journal of Allergy and Clinical Immunology 2018 142, 1346-1349.e9DOI: (10.1016/j.jaci.2018.05.033) Copyright © 2018 The Authors Terms and Conditions