Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells
| Autor: | Graham Anderson, Izumi Ohigashi, William E. Jenkinson, Andrea J. White, Beth Lucas, Kieran D. James, Nick D. Jones, Emilie J. Cosway, Sonia M. Parnell, Yousuke Takahama |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
T-Lymphocytes Science T cell General Physics and Astronomy Thymus Gland Biology Lymphocyte Activation Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Antigen Lymphotoxin beta Receptor medicine Animals Cell Lineage lcsh:Science Cell Proliferation Mice Knockout Mice Inbred BALB C Thymocytes Multidisciplinary Cell growth Effector Cell Differentiation Epithelial Cells Dendritic Cells General Chemistry Natural killer T cell Thymus Cell biology Mice Inbred C57BL NKT cells 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Clonal selection Cytokines Natural Killer T-Cells lcsh:Q Antigens CD1d Intracellular Function (biology) Signal Transduction 030215 immunology CCL21 |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The thymus supports multiple αβ T cell lineages that are functionally distinct, but mechanisms that control this multifaceted development are poorly understood. Here we examine medullary thymic epithelial cell (mTEC) heterogeneity and its influence on CD1d-restricted iNKT cells. We find three distinct mTEClow subsets distinguished by surface, intracellular and secreted molecules, and identify LTβR as a cell-autonomous controller of their development. Importantly, this mTEC heterogeneity enables the thymus to differentially control iNKT sublineages possessing distinct effector properties. mTEC expression of LTβR is essential for the development thymic tuft cells which regulate NKT2 via IL-25, while LTβR controls CD104+CCL21+ mTEClow that are capable of IL-15-transpresentation for regulating NKT1 and NKT17. Finally, mTECs regulate both iNKT-mediated activation of thymic dendritic cells, and iNKT availability in extrathymic sites. In conclusion, mTEC specialization controls intrathymic iNKT cell development and function, and determines iNKT pool size in peripheral tissues. Thymus is a unique environment hosting the development of many T cell subsets with distinct functions. Here the authors show that medullary thymic epithelial cells (mTEC) are functionally diverse, with LTβR signaling serving differential regulation of mTEC for specific control of multiple lineages of invariant natural killer T cells. |
| Databáze: | OpenAIRE |
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