Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing

Abstract

Lymphocytes are recruited from blood by high-endothelial venules (HEVs). We performed transcriptomic analyses and identified molecular signatures that distinguish HEVs from capillary endothelium and that define tissue-specific HEV specialization. Capillaries displayed gene programs for vascular development. HEVs were enriched in genes for immune defense and lymphocyte migration. We identify capillary and HEV markers and candidate mechanisms for regulated lymphocyte recruitment including a lymph node HEV-selective transmembrane mucin; transcriptional control of functionally specialized carbohydrate ligands for lymphocyte L-selectin; HEV expression of molecules for transendothelial migration; and metabolic programs for lipid mediators of lymphocyte motility and chemotaxis. We also elucidate a carbohydrate recognition pathway that targets B cells to intestinal lymphoid tissues, defining CD22 as a lectin-homing receptor for mucosal HEVs.

Absence of Nkx2-3 Homeodomain Transcription Factor Reprograms the Endothelial Addressin Preference for Lymphocyte Homing in Peyer’s Patches

“…Consistent with this proposal, transcripts for Nkx2-3 are highly expressed in PPs and mLN high endothelial cells, but only minimally expressed in normal adult pLN high endothelium. Interestingly, although in wild-type mice endothelial cells of both HEVs and non-HEV capillaries within PPs express Nkx2-3 mRNA, only HEV endothelial cells display MAdCAM-1, indicating subtle differences between the impacts of Nkx2-3 expression between various elements of local vasculature (15). The occurrence of MAdCAM-1 + PNAd + vessels in postnatal PPs in Nkx2-3 mutants suggests that the PNAd + HEVs in adults develop from the MAdCAM-1 + segments and not from MAdCAM-1 2 capillaries.…”

“…Nkx2-3 transcripts are expressed in PPs and mLNs but only marginally in pLN high endothelial cells (15), and they thus are likely to act cell-intrinsically within HEVs to regulate MAdCAM-1 expression, although indirect effects through stromal or epithelial cell signals are not excluded. In spleen the absence of Nkx2-3 causes severe structural alterations of the marginal zone, follicles (16,17), and the pattern of vasculature particularly affecting the red pulp (18).…”

Novel Antibodies Reactive with Sialyl Lewis X in Both Humans and Mice Define Its Critical Role in Leukocyte Trafficking and Contact Hypersensitivity Responses

“…Therefore, these findings collectively suggest that unsulfated sLe x structure plays an important role in lymphocyte homing to PPs. The residual homing to PP in the presence of F1 or F2 could be due to ␣4␤7 integrin and MAd-CAM-1 interaction (27) or CD22-mediated homing of B cells (28).…”

Patterns of expression of factor VIII and von Willebrand factor by endothelial cell subsets in vivo

“…The fluorescence-activated cell sorted EC subsets were placed directly into RNA lysis buffer, followed by total RNA isolation and microarray-based transcriptomic profiling as described. 14 …”