Coordinated transcriptional networks program organelle expansion and metabolic flows for high endothelial morphology and function.

Endothelial-specific deletion of Xbp1 impairs organelle expansion, reduces PNAd expression, and disrupts lymphocyte recruitment in high endothelial cells.

• Why it matters: Understanding how HEC morphology and function are coordinated is crucial for insights into immune cell trafficking and inflammatory responses, filling a key knowledge gap.
• What they did: The study used gene enrichment analysis, transcription factor binding assays, and genetic or pharmacologic inhibition of XBP1 and CREB3L2 to investigate their roles in HECs, focusing on sulfo- and fucosyl-transferase genes.
• The result: Findings reveal that ER stress-response transcription factors XBP1 and CREB3L2 regulate organelle expansion and sulfoglycoprotein synthesis, enabling HECs to maintain their specialized morphology and immune functions.