CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3(+) T Cells

Cell Rep. 2016 Feb 9;14(5):1041-1048. doi: 10.1016/j.celrep.2016.01.003. Epub 2016 Jan 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement*
  • Forkhead Transcription Factors / metabolism*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, CCR6 / metabolism
  • Receptors, CCR7 / metabolism*
  • T-Lymphocytes, Regulatory / cytology
  • Thymus Gland / cytology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, CCR6
  • Receptors, CCR7