First Author | White AJ | Year | 2017 |
Journal | J Exp Med | Volume | 214 |
Issue | 8 | Pages | 2205-2216 |
PubMed ID | 28694386 | Mgi Jnum | J:244426 |
Mgi Id | MGI:5913205 | Doi | 10.1084/jem.20170271 |
Citation | White AJ, et al. (2017) A type 2 cytokine axis for thymus emigration. J Exp Med 214(8):2205-2216 |
abstractText | 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-4Ralpha 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-4Ralpha 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-4Ralpha 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. |