A type 2 cytokine axis for thymus emigration

Research output: Contribution to journalArticle

Colleges, School and Institutes

External organisations

  • Institute for Immunology and Immunotherapy, College of Medical and Dental Sciences, Medical School, University of Birmingham, Birmingham, England, UK.
  • International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Institute of Infectious Diseases and Molecular Medicine and South African Medical Research Council, University of Cape Town, Cape Town, South Africa.
  • Institute for Immunology and Immunotherapy, College of Medical and Dental Sciences, Medical School, University of Birmingham, Birmingham, England, UK g.anderson@bham.ac.uk.

Abstract

In the thymus, stromal microenvironments support a developmental program that generates mature T cells ready for thymic exit. The cellular and molecular specialization within thymic stromal cells that enables their regulation of specific stages of thymocyte development is poorly understood. Here, we show the thymic microenvironment expresses the type 2 IL-4R complex and is functionally responsive to its known ligands, IL-4 and IL-13. Absence of IL-4Rα limits thymocyte emigration, leading to an intrathymic accumulation of mature thymocytes within medullary perivascular spaces and reduced numbers of recent thymic emigrants. Thymus transplantation shows this requirement maps to IL-4Rα expression by stromal cells, and we provide evidence that it regulates thymic exit via a process distinct from S1P-mediated migration. Finally, we reveal a cellular mechanism by which IL-4(+)IL-13(+) invariant NKT cells are necessary for IL-4Rα signaling that regulates thymic exit. Collectively, we define a new axis for thymic emigration involving stimulation of the thymic microenvironment via type 2 cytokines from innate T cells.

Details

Original languageEnglish
JournalThe Journal of Experimental Medicine
Volume214
Issue number7
Publication statusPublished - 10 Jul 2017