The thymus is a heterogeneous mix of hematopoietic and stromal cells that function to generate a functional, self-tolerant T-cell pool. Although many of these populations are well studied, the role of non-epithelial stroma remains unclear. Thymic mesenchyme has been identified as an important regulator of T-cell egress. Studies of lymphotoxin beta-receptor LTβR have revealed its critical role in T-cell egress as well as the development and function of lymph node mesenchyme. We hypothesized that LTβR regulation of thymic mesenchyme is critical forT-cell egress. To test this we generated \(Wnt-1^{cre}Ltbr^{flox}\) mice to delete LTβR on thymic mesenchyme and revealed this to be non-essential forT-cell egress. Moreover, we generated \(Foxn-1^{cre}Ltbr^{flox}\) mice to delete LTβR on thymic epithelial cell (TEC). Despite the critical role of LTβR in medullary TEC development, T-cell egress was normal. However, deleting LTβR on thymic endothelium using \(Flk-1^{cre}Ltbr^{flox}\) mice revealed an essential role of LTβR regulation of endothelium to control T-cell egress. Our analysis also revealed that T-cell entry into the perivascular space during T-cell egress occurs stochastically. Collectively our findings highlight a novel role for LTβR regulation of thymic endothelium as a critical pathway of T-cell egress.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:742578 |
| Date | January 2018 |
| Creators | James, Kieran David Jon |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/8051/ |
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