Absence of Nkx2-3 homeodomain transcription factor reprograms the endothelial addressin preference for lymphocyte homing in peyer's patches

Zoltán Kellermayer, Martina Mihalj, Árpád Lábadi, T. Czömpöly, Mike Lee, Edward O'Hara, Eugene C. Butcher, Gergely Berta, András Balogh, Hans Henning Arnold, P. Balogh

Research output: Article

7 Citations (Scopus)

Abstract

Although the homing of lymphocytes to GALT has been extensively studied, little is known about how high endothelial venules (HEVs) within Peyer's patches (PPs) are patterned to display dominantly mucosal addressin cell adhesion molecule 1 (MAdCAM-1). In this study, we report that Nkx2-3-deficient mice show gradual loss of MAdCAM-1 in PPs postnatally and increased levels of mRNA for peripheral lymph node addressin (PNAd) backbone proteins as well as enhanced expression of MECA79 sulfated glycoepitope at the luminal aspect of HEVs, thus replacing MAdCAM-1 with PNAd. Induction of PNAd in mutant PPs requires lymphotoxin b receptor activity, and its upregulation needs the presence of mature T and B cells. Furthermore, treatment with MECA-79 anti-PNAd mAb in vivo effectively blocks lymphocyte homing to mutant PPs. Despite the replacement of MAdCAM-1 by PNAd in HEV endothelia, lymphocytes could efficiently home to PPs in mutant mice.We conclude that although Nkx2-3 activity controls the addressin balance of HEVs in GALT, the general HEV functionality is preserved independently from Nkx2-3, indicating a substantial plasticity in the specification of GALT HEV endothelium.

Original languageEnglish
Pages (from-to)5284-5293
Number of pages10
JournalJournal of Immunology
Volume193
Issue number10
DOIs
Publication statusPublished - nov. 15 2014

Fingerprint

Transcription Factor 3
Peyer's Patches
Venules
Cell Adhesion Molecules
Lymphocytes
Endothelium
Lymphotoxin-alpha
L-selectin counter-receptors
B-Lymphocytes
Up-Regulation
T-Lymphocytes
Messenger RNA

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Absence of Nkx2-3 homeodomain transcription factor reprograms the endothelial addressin preference for lymphocyte homing in peyer's patches. / Kellermayer, Zoltán; Mihalj, Martina; Lábadi, Árpád; Czömpöly, T.; Lee, Mike; O'Hara, Edward; Butcher, Eugene C.; Berta, Gergely; Balogh, András; Arnold, Hans Henning; Balogh, P.

In: Journal of Immunology, Vol. 193, No. 10, 15.11.2014, p. 5284-5293.

Research output: Article

Kellermayer, Zoltán ; Mihalj, Martina ; Lábadi, Árpád ; Czömpöly, T. ; Lee, Mike ; O'Hara, Edward ; Butcher, Eugene C. ; Berta, Gergely ; Balogh, András ; Arnold, Hans Henning ; Balogh, P. / Absence of Nkx2-3 homeodomain transcription factor reprograms the endothelial addressin preference for lymphocyte homing in peyer's patches. In: Journal of Immunology. 2014 ; Vol. 193, No. 10. pp. 5284-5293.
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