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  • Title: CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3(+) T Cells.
    Author: Cowan JE, McCarthy NI, Anderson G.
    Journal: Cell Rep; 2016 Feb 09; 14(5):1041-1048. PubMed ID: 26832402.
    Abstract:
    Current models of Foxp3(+) regulatory T cell (Treg) development involve CCR7-mediated migration of thymocytes into the thymus medulla to enable essential interactions with medullary epithelium. However, increased Foxp3(+) thymic Treg numbers in Ccr7(-/-) mice challenge this view, and the role of CCR7 in Treg development, emigration, and/or recirculation is unknown. Here, we have examined CCR7 and Rag2pGFP levels during Treg development and generated Rag2pGFPCcr7(-/-) mice to study its impact on the intrathymic Treg pool. We reveal surprising developmental heterogeneity in thymocytes described as Treg precursors, showing that they contain recirculating CCR6(+)CCR7(-)Rag2pGFP(-) T cells. Although CCR7 defines bona fide Rag2GFP(+) Treg precursors, it is not required for Treg production and emigration. Rather, we show that lack of CCR7 renders the thymus more receptive to Treg thymus homing. Our study reveals a role for CCR7 in limiting Treg recirculation back to the thymus and enables separation of the mechanisms controlling Treg production and thymic recirculation.
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