title: Absence of Nkx2-3 homeodomain transcription factor reprograms the endothelial addressin preference for lymphocyte homing in Peyer's patches.
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 β 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.
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pécs, H-7624 Pécs, Hungary; Lymphoid Organogenesis Research Group, Szentágothai János Research Center, University of Pécs, H-7624 Pécs, Hungary;
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kellermayer
authors.affiliation: Department of Physiology and Immunology, University of Osijek, 31000 Osijek, Croatia;
authors.forename: Martina
authors.initials: M
authors.lastname: Mihalj
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pécs, H-7624 Pécs, Hungary;
authors.forename: Árpád
authors.initials: Á
authors.lastname: Lábadi
authors.affiliation: Cancer Research and Product Development Laboratory, Immunal Ltd., H-7630 Pécs, Hungary;
authors.forename: Tamás
authors.initials: T
authors.lastname: Czömpöly
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305;
authors.forename: Mike
authors.initials: M
authors.lastname: Lee
authors.affiliation: Palo Alto Veterans Institute for Research, Palo Alto, CA 94304;
authors.forename: Edward
authors.initials: E
authors.lastname: O'Hara
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305; Palo Alto Veterans Institute for Research, Palo Alto, CA 94304; Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304;
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
authors.affiliation: Department of Medical Biology, University of Pécs, H-7624 Pécs, Hungary; and.
authors.forename: Gergely
authors.initials: G
authors.lastname: Berta
authors.affiliation: Department of Medical Biology, University of Pécs, H-7624 Pécs, Hungary; and.
authors.forename: András
authors.initials: A
authors.lastname: Balogh
authors.affiliation: Department of Cell and Molecular Biology, Institute of Biochemistry and Biotechnology, Technical University of Braunschweig, 38106 Braunschweig, Germany.
authors.forename: Hans-Henning
authors.initials: HH
authors.lastname: Arnold
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pécs, H-7624 Pécs, Hungary; Lymphoid Organogenesis Research Group, Szentágothai János Research Center, University of Pécs, H-7624 Pécs, Hungary; balogh.peter@pte.hu.
authors.forename: Péter
authors.initials: P
authors.lastname: Balogh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009088:Mucoproteins; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D014699:Venules / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D018398:Homeodomain Proteins; C069886:L-selectin counter-receptors; D053259:Lymphotoxin beta Receptor; C489082:Madcam1 protein, mouse; D008565:Membrane Proteins; D009088:Mucoproteins; C522706:Nkx2.3 protein, mouse; D014157:Transcription Factors