Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface.

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  • Author(s): Nancy P;Nancy P; Tagliani E; Tay CS; Asp P; Levy DE; Erlebacher A
  • Source:
    Science (New York, N.Y.) [Science] 2012 Jun 08; Vol. 336 (6086), pp. 1317-21.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
    • Publication Information:
      Publication: : Washington, DC : American Association for the Advancement of Science
      Original Publication: New York, N.Y. : [s.n.] 1880-
    • Subject Terms:
      Gene Silencing* ; Immune Tolerance*; Chemokines/*genetics ; Decidua/*immunology ; Decidua/*metabolism ; Stromal Cells/*immunology ; Stromal Cells/*metabolism ; T-Lymphocyte Subsets/*immunology; Animals ; Chemokine CCL5/genetics ; Chemokine CCL5/metabolism ; Chemokine CXCL10/genetics ; Chemokine CXCL10/metabolism ; Chemokine CXCL11/genetics ; Chemokine CXCL11/metabolism ; Chemokine CXCL9/genetics ; Chemokine CXCL9/metabolism ; Chemokines/metabolism ; Chromatin Immunoprecipitation ; Endometrium/cytology ; Endometrium/immunology ; Female ; Histones/metabolism ; Immunologic Memory ; Inflammation ; Methylation ; Mice ; Mice, Inbred C57BL ; Myometrium/immunology ; Ovalbumin/immunology ; Pregnancy ; Promoter Regions, Genetic ; Receptors, CXCR3/immunology ; Receptors, CXCR3/metabolism
    • Abstract:
      The chemokine-mediated recruitment of effector T cells to sites of inflammation is a central feature of the immune response. The extent to which chemokine expression levels are limited by the intrinsic developmental characteristics of a tissue has remained unexplored. We show in mice that effector T cells cannot accumulate within the decidua, the specialized stromal tissue encapsulating the fetus and placenta. Impaired accumulation was in part attributable to the epigenetic silencing of key T cell-attracting inflammatory chemokine genes in decidual stromal cells, as evidenced by promoter accrual of repressive histone marks. These findings give insight into mechanisms of fetomaternal immune tolerance, as well as reveal the epigenetic modification of tissue stromal cells as a modality for limiting effector T cell trafficking.
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    • Grant Information:
      P30 CA016087 United States CA NCI NIH HHS; R01 AI062980 United States AI NIAID NIH HHS; R01AI062980 United States AI NIAID NIH HHS; P30CA016087 United States CA NCI NIH HHS
    • Accession Number:
      0 (Ccl5 protein, mouse)
      0 (Chemokine CCL5)
      0 (Chemokine CXCL10)
      0 (Chemokine CXCL11)
      0 (Chemokine CXCL9)
      0 (Chemokines)
      0 (Cxcl10 protein, mouse)
      0 (Cxcl9 protein, mouse)
      0 (Cxcr3 protein, mouse)
      0 (Histones)
      0 (Receptors, CXCR3)
      9006-59-1 (Ovalbumin)
    • Publication Date:
      Date Created: 20120609 Date Completed: 20120626 Latest Revision: 20211021
    • Publication Date:
      20231215
    • Accession Number:
      PMC3727649
    • Accession Number:
      10.1126/science.1220030
    • Accession Number:
      22679098