Distinct roles of lymphotoxin-β signaling and the homeodomain transcription factor Nkx2.3 in the ontogeny of endothelial compartments in spleen

Péter Balogh, Mercedesz Balázs, Tamás Czömpöly, Debra S. Weih, Hans Henning Arnold, Falk Weih

Research output: Article

13 Citations (Scopus)

Abstract

The formation of peripheral lymphoid tissues is indispensable for the efficient recognition and elimination of external antigens by lymphoid and accessory cells of the adaptive immune system. The spleen is structurally arranged around various vascular beds with distinct endothelial phenotypes. Using immunohistochemistry, we investigated the postnatal developmental characteristics of the marginal sinus and its relationship with various red-pulp sinus subsets. We also determined the importance of the lymphotoxin β receptor (LTβR) and the role of the Nkx2.3 transcription factor for the formation of the splenic vasculature. Both the administration of soluble LTβR-Ig fusion protein to neonates and the deletion of LTβR or downstream signaling components (RelB and p52) of the NF-κB family inhibited the phenotypic maturation of marginal sinus but had no effect on the vascular compartmentalization of the red pulp. The integrity of the marginal sinus and the proper vascular segregation of the red pulp appeared to be controlled by Nkx2.3, as Nkx2.3-deficient mice exhibited an abnormal distribution of IBL-7/1hi/IBL-9/2- sinuses and a lack of IBL-7/1lo/IBL-9/2+ vessels. Our data suggest that phenotypic heterogeneity among different vascular elements within distinct anatomical regions of the spleen differentially depends on developmental factors such as lymphotoxin signaling or Nkx2.3, whereas the marginal sinus is controlled by both pathways.

Original languageEnglish
Pages (from-to)473-486
Number of pages14
JournalCell And Tissue Research
Volume328
Issue number3
DOIs
Publication statusPublished - jún. 1 2007

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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