Investigating the process and regulation of thymocyte egress by lymphotoxin beta receptor and thymic stroma

[摘要] 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 (LT\(\beta\)R) have revealed its critical role in T-cell egress as well as the development and function of lymph node mesenchyme. We hypothesized that (LT\(\beta\)R) regulation of thymic mesenchyme is critical forT-cell egress. To test this we generated \(Wnt-1^{cre}Ltbr^{flox}\) mice to delete (LT\(\beta\)R) on thymic mesenchyme and revealed this to be non-essential forT-cell egress. Moreover, we generated \(Foxn-1^{cre}Ltbr^{flox}\) mice to delete (LT\(\beta\)R) on thymic epithelial cell (TEC). Despite the critical role of (LT\(\beta\)R) in medullary TEC development, T-cell egress was normal. However, deleting (LT\(\beta\)R) on thymic endothelium using \(Flk-1^{cre}Ltbr^{flox}\) mice revealed an essential role of (LT\(\beta\)R) 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 (LT\(\beta\)R) regulation of thymic endothelium as a critical pathway of T-cell egress.

[发布机构] University:University of Birmingham;Department:Institute of Immunology and Immunotherapy

[关键词] Q Science;QR Microbiology;QR180 Immunology