“Mechanisms underlying the epigenetic reprogramming of innate immune cells during Western Diet feeding”

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Dec. 13, 2018 from 2 p.m. to 3 p.m.

Address
Hess 2nd Floor – Seminar Room A
Hess Center for Science & Medicine
1470 Madison Avenue
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Speakers
  • Anette Christ, PhD
  • UMass Medical School
  • Department of Medicine
  • Division for Infectious Diseases and Immunology
  • Institute for Innate Immunity Biomedical Center
  • University Hospital Bonn, Germany
RSVP

Abstract: Sustained epigenetic reprogramming of innate immune cells in response to pathogens, termed ’trained immunity’ or ’innate immune memory’, beneficially converts cellular functionality to protect from secondary infections. However, inappropriate activation of immunological imprinting mediated by ’trained immunity’ may contribute to reinforced immune responses in inflammatory diseases, such as type 2 diabetes, obesity and cardiovascular diseases (CVDs). Given the above hypothesis, we previously investigated whether a hyperlipidemic environment can considerably modify innate immune cell gene signatures, thus evoking a condition of continuous immune cell activation. Using the Ldlr-/- hypercholesterolemia mouse model, we discovered that a short period of Western diet (WD) feeding resulted in a transient systemic inflammatory response, yet induces long-lasting transcriptomic and epigenomic reprogramming of myeloid cells, which led to immune cell hyper-responsiveness upon subsequent immune stimulation. These data suggest that WD is capable of inducing trained immunity and that the immune system misinterprets WD as a pathogenic infection. Recently, several reports have documented the detrimental effect of ‘Western-type’ diets on gut microbial composition, the impact on local and systemic immune responses and a potential link to CVDs. Alltogether, these findings still raise the questions how and on which level dietary intake, NLRP3 activation, subsequent IL-1 signaling and long-term hematopoietic myeloid progenitor reprogramming are interrelated. At the moment, we are assessing, if WD-induced alterations in the intestinal microbiome and microbiome-associated metabolites are impacting the cellular metabolism and signaling pathways in tissue-resident macrophage subsets in different metabolic organs, as well as in hematopoietic stem cells, thus leading to sustained epigenetic modifications. Beside, we are examining, whether the WD-induced myeloid progenitor reprogramming can be modulated/ reversed by epigenetic enzyme inhibitors.

ADDRESS

  • Address: Leon and Norma Hess Center for Science and Medicine 1470 Madison Avenue (between 101st and 102nd St) TMII - 1st Floor New York,
    NY 10029
  • Email: TMII@mssm.edu
  • Website: tmii.mssm.edu
  • Tel: (212) 824-8471
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