Progesterone impairs antigen-non-specific immune protection by CD8 T memory cells via interferon-γ gene hypermethylation
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{"title"=>"Progesterone impairs antigen-non-specific immune protection by CD8 T memory cells via interferon-γ gene hypermethylation", "type"=>"journal", "authors"=>[{"first_name"=>"Yushi", "last_name"=>"Yao", "scopus_author_id"=>"54882573500"}, {"first_name"=>"Hui", "last_name"=>"Li", "scopus_author_id"=>"57198448006"}, {"first_name"=>"Jie", "last_name"=>"Ding", "scopus_author_id"=>"57200583504"}, {"first_name"=>"Yixin", "last_name"=>"Xia", "scopus_author_id"=>"57198451262"}, {"first_name"=>"Lei", "last_name"=>"Wang", "scopus_author_id"=>"57196334789"}], "year"=>2017, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"85036535622", "doi"=>"10.1371/journal.ppat.1006736", "pui"=>"619529374", "pmid"=>"29155896", "scopus"=>"2-s2.0-85036535622", "issn"=>"15537374", "isbn"=>"1111111111"}, "id"=>"c2fc46ca-830c-3e48-9777-a5ef410cc9de", "abstract"=>"Pregnant women and animals have increased susceptibility to a variety of intracellular pathogens including Listeria monocytogenes (LM), which has been associated with significantly increased level of sex hormones such as progesterone. CD8 T memory(Tm) cell-mediated antigen-non-specific IFN-γ responses are critically required in the host defense against LM. However, whether and how increased progesterone during pregnancy modulates CD8 Tm cell-mediated antigen-non-specific IFN-γ production and immune protection against LM remain poorly understood. Here we show in pregnant women that increased serum progesterone levels are associated with DNA hypermethylation of IFN-γ gene promoter region and decreased IFN-γ production in CD8 Tm cells upon antigen-non-specific stimulation ex vivo. Moreover, IFN-γ gene hypermethylation and significantly reduced IFN-γ production post LM infection in antigen-non-specific CD8 Tm cells are also observed in pregnant mice or progesterone treated non-pregnant female mice, which is a reversible phenotype following demethylation treatment. Importantly, antigen-non-specific CD8 Tm cells from progesterone treated mice have impaired anti-LM protection when adoptive transferred in either pregnant wild type mice or IFN-γ-deficient mice, and demethylation treatment rescues the adoptive protection of such CD8 Tm cells. These data demonstrate that increased progesterone impairs immune protective functions of antigen-non-specific CD8 Tm cells via inducing IFN-γ gene hypermethylation. Our findings thus provide insights into a new mechanism through which increased female sex hormone regulate CD8 Tm cell functions during pregnancy.", "link"=>"http://www.mendeley.com/research/progesterone-impairs-antigennonspecific-immune-protection-cd8-t-memory-cells-via-interferon%CE%B3-gene-hy", "reader_count"=>6, "reader_count_by_academic_status"=>{"Researcher"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

Scopus | Further Information

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