| First Author | Wang Z | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 1 | Pages | 69-76 |
| PubMed ID | 29760194 | Mgi Jnum | J:263332 |
| Mgi Id | MGI:6164071 | Doi | 10.4049/jimmunol.1701080 |
| Citation | Wang Z, et al. (2018) Differential Roles of LTbetaR in Endothelial Cell Subsets for Lymph Node Organogenesis and Maturation. J Immunol 201(1):69-76 |
| abstractText | Cellular cross-talk mediated by lymphotoxin alphabeta-lymphotoxin beta receptor (LTbetaR) signaling plays a critical role in lymph node (LN) development. Although the major role of LTbetaR signaling has long been considered to occur in mesenchymal lymphoid tissue organizer cells, a recent study using a VE-cadherin(cre)Ltbr(fl/fl) mouse model suggested that endothelial LTbetaR signaling contributes to the formation of LNs. However, the detailed roles of LTbetaR in different endothelial cells (ECs) in LN development remain unknown. Using various cre transgenic mouse models (Tek(cre) , a strain targeting ECs, and Lyve1(cre) , mainly targeting lymphatic ECs), we observed that specific LTbetaR ablation in Tek(cre+) or Lyve1(cre+) cells is not required for LN formation. Moreover, double-cre-mediated LTbetaR depletion does not interrupt LN formation. Nevertheless, Tek(cre)Ltbr(fl/fl) mice exhibit reduced lymphoid tissue inducer cell accumulation at the LN anlagen and impaired LN maturation. Interestingly, a subset of ECs (VE-cadherin(+)Tek(cre-low/neg) ECs) was found to be enriched in transcripts related to hematopoietic cell recruitment and transendothelial migration, resembling LN high ECs in adult animals. Furthermore, endothelial Tek was observed to negatively regulate hematopoietic cell transmigration. Taken together, our data suggest that although Tek(cre+) endothelial LTbetaR is required for the accumulation of hematopoietic cells and full LN maturation, LTbetaR in VE-cadherin(+)Tek(cre-low/neg) ECs in embryos might represent a critical portal-determining factor for LN formation. |
