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The sexually dimorphic histone demethylase promotes optimal T cell responses during infection
Presentation Time: 08:45 AM - 09:00 AM
Abstract ID: 5745 - B
Presenting Author: Connie Krawczyk
, Associate Professor at Van Andel Inst.
Abstract:
Females have stronger immune responses than males. This can be a protective benefit for immune responses to infection and cancer, but also a detriment for the development of autoimmune disease. The genetic contributions to sexually dimorphic immunity are not well understood. We have identified the X-linked histone demethylase KDM5C as an important regulator of T cell immunity. KDM5C escapes X inactivation so is expressed more in females than males. KDM5C demethylates H3K4, participating in gene silencing, however also has a role in promoting gene expression. Mice deficient in KDM5C in immune cells have reduced ability to control acute and chronic infection. Intrinsic KDM5C expression in CD8 T cells is required for their expansion and function. Mechanistically, we find that KDM5C regulates the expression of key metabolic proteins that support T cell function. Collectively, our data suggests that KDM5C promotes a bioenergetic/anabolic metabolic program that improves the metabolic fitness and function of activated CD8 T cells, thereby supporting CD8 T cell - mediated immunity. These data implicate KDM5C as an important promoter of T cell immunity and is a potential mechanism underpinning sexual dimorphic immune responses to infection.
The sexually dimorphic histone demethylase promotes optimal T cell responses during infection
Category
Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 08:45 AM to 09:00 AM Room: Room W185