title: CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3(+) T Cells.
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.
authors.affiliation: MRC Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cowan
authors.affiliation: MRC Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: McCarthy
authors.affiliation: MRC Centre for Immune Regulation, Institute for Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK. Electronic address: g.anderson@bham.ac.uk.
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054399:Receptors, CCR6 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D054399:Receptors, CCR6; D054400:Receptors, CCR7
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