Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface.
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.
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Patrice
P
Nancy
Elisa
E
Tagliani
Chin-Siean
CS
Tay
Patrik
P
Asp
David E
DE
Levy
Adrian
A
Erlebacher
D000818:Animals; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000235:genetics / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D003656:Decidua / Q000276:immunology* / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology / Q000276:immunology; D005260:Female; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D007108:Immune Tolerance; D007156:Immunologic Memory; D007249:Inflammation; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D009215:Myometrium / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D054367:Receptors, CXCR3 / Q000276:immunology / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D018925:Chemokines; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; C515188:Cxcr3 protein, mouse; D006657:Histones; D054367:Receptors, CXCR3; D010047:Ovalbumin