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Epigenetic Influences on Bovine T-helper 1 and T-helper 2 Cytokines (Interferon-gamma and Interleukin-4) in High and Low Immune Responders around the Peripartum Period

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Title: Epigenetic Influences on Bovine T-helper 1 and T-helper 2 Cytokines (Interferon-gamma and Interleukin-4) in High and Low Immune Responders around the Peripartum Period
Author: Paibomesai, Marlene Ann
Department: Department of Pathobiology
Program: Pathobiology
Advisor: Mallard, Bonnie A.
Abstract: Livestock epigenetics has applications in the areas of disease biomarkers and drug development, as well as animal breeding. The objectives of this research were: 1- investigate DNA methylation at the type 1 cytokine interferon gamma (IFN-γ) and the type 2 cytokine interleukin 4 (IL-4) promoter regions of CD4+ T-cells isolated from dairy cows, and 2- determine production of type 1 and type 2 cytokines across the peripartum period from antibody- (AMIR) or cell-mediated immune response (CMIR) biased cows as it relates to DNA methylation of IFN-γ and IL-4. Cows were ranked according to immune response phenotype by High Immune Response® testing, which evaluates AMIR and CMIR with type 1 and type 2 antigens, through which cows were ranked high (H), average (A), and low (L) immune responders. Cows either possessed a bias towards H-AMIR with L-CMIR (n=11) or H-CMIR with L-AMIR (n=10). Peripartum CD4+ T-cells were isolated at -28 days, +4 days and +21 days from calving and stimulated with ConcanavalinA for 24 hours. CD4+ T-cell cytokines were determined for IFN-γ, IL-4, and IL17A from cultured cells and DNA samples were taken for assessment of DNA methylation by bisulfite pyrosequencing. Cows that were biased towards an H-CMIR phenotype produced more cytokine (IFN-γ, IL-4, and IL-17A) at +21 days from calving than H-AMIR cows and generally more cytokine than prepartum CD4+ T-cell samples. There were differences in cytokine methylation at individual CpG sites across the promoter regions for IFN-γ or IL-4, including: IFN-γ CpG+57 from the transcription start site (-6.6%), IFN-γ CpG+72(-15%) and IL-4 CpG+128 (-9%) between H-CMIR and H-AMIR cows. Individual CpG site differences were evident in CD4+ T-cells sampled pre- (-28 days) and post-partum (+21 days): IFN-γ CpG+57 (-13%), IFN-γ CpG+72 (-17%), IL-4 CpG+128 (-15%), IL-4 CpG+175(-23%) and IL-4 CpG+193 (-11%). This was associated with elevated cytokine production postpartum. This thesis supports an association of DNA methylation with bovine CD4+ T-cell cytokine production and that immune response phenotype is associated with changes in DNA methylation at IFN-γ and IL-4 promoters.
URI: http://hdl.handle.net/10214/10217
Date: 2017-01
Rights: Attribution 2.5 Canada


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Attribution 2.5 Canada Except where otherwise noted, this item's license is described as Attribution 2.5 Canada