A type 2 cytokine axis for thymus emigration

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...

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Bibliographic Details
Published in:	The Journal of experimental medicine 2017-08, Vol.214 (8), p.2205-2216
Main Authors:	White, Andrea J, Baik, Song, Parnell, Sonia M, Holland, Amanda M, Brombacher, Frank, Jenkinson, William E, Anderson, Graham
Format:	Article
Language:	eng
Subjects:	Animals Cell migration Cell Movement - physiology Cytokines Developmental stages Emigration Interleukin 13 Interleukin 4 Interleukin-13 - physiology Interleukin-4 - physiology Invariants Leukocyte migration Lymphocytes Lymphocytes T Mice Mice, Knockout Microenvironments Natural killer cells Natural Killer T-Cells - physiology Receptors, Interleukin-4 - physiology Signal Transduction - physiology Signaling Specialization Stromal cells T cell receptors Thymocytes Thymocytes - physiology Thymus Thymus Gland - physiology Thymus Gland - transplantation Transplantation
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Summary:	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.
ISSN:	0022-1007 1540-9538