Differential Roles of LTβR in Endothelial Cell Subsets for Lymph Node Organogenesis and Maturation

The Journal of Immunology : Official Journal of the American Association of Immunologists
Zhongnan WangMingzhao Zhu

Abstract

Cellular cross-talk mediated by lymphotoxin αβ-lymphotoxin β receptor (LTβR) signaling plays a critical role in lymph node (LN) development. Although the major role of LTβR signaling has long been considered to occur in mesenchymal lymphoid tissue organizer cells, a recent study using a VE-cadherincreLtbrfl/fl mouse model suggested that endothelial LTβR signaling contributes to the formation of LNs. However, the detailed roles of LTβR in different endothelial cells (ECs) in LN development remain unknown. Using various cre transgenic mouse models (Tekcre , a strain targeting ECs, and Lyve1cre , mainly targeting lymphatic ECs), we observed that specific LTβR ablation in Tekcre+ or Lyve1cre+ cells is not required for LN formation. Moreover, double-cre-mediated LTβR depletion does not interrupt LN formation. Nevertheless, TekcreLtbrfl/fl mice exhibit reduced lymphoid tissue inducer cell accumulation at the LN anlagen and impaired LN maturation. Interestingly, a subset of ECs (VE-cadherin+Tekcre-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 hematopo...Continue Reading

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Citations

Apr 13, 2019·Immunological Reviews·Nadine EckertReinhold Förster
Apr 7, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhongnan WangMingzhao Zhu
Sep 5, 2018·European Journal of Immunology·Tom Cupedo
Apr 15, 2021·Biomedical Journal·Serge A van de Pavert
Jul 8, 2019·Annals of Anatomy = Anatomischer Anzeiger : Official Organ of the Anatomische Gesellschaft·Lucio Díaz-FloresJosé Luis Carrasco

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