NKX2.3 is required for MAdCAM-1 expression and homing of lymphocytes in spleen and mucosa-associated lymphoid tissue

Item Type:	Article
Title:	NKX2.3 is required for MAdCAM-1 expression and homing of lymphocytes in spleen and mucosa-associated lymphoid tissue
Creators Name:	Pabst, O. and Foerster, R. and Lipp, M. and Engel, H. and Arnold, H.H.
Abstract:	Targeted disruption of the transcription factor NKX2.3 gene in mice results in anatomical defects of intestine and secondary lymphoid organs. Here, we report that spleen and Peyer's patches of NKX2.3-deficient mice are considerably reduced in size and lack the ordered tissue architecture. T and B cells are misplaced within the spleen and mesenteric lymph nodes and fail to segregate into the appropriate T and B cell areas. Furthermore, splenic marginal zones, characterized by specific B cells and various types of macrophage-derived cells around the marginal sinus, are absent in mutants. Homozygous NKX2.3 mutants lack the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that is normally expressed in mucosa-associated lymphoid tissue (MALT) and spleen. We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly, suggesting that MAdCAM-1 is at least partly responsible for the migration and homing defects of lymphocytes and macrophages in mutants. Therefore, expression of MAdCAM-1 seems to be required for building functional structures in spleen and MALT, a prerequisite for unimpaired migration and segregation of B and T cells to and within these organs.
Keywords:	Lymphocyte Homing, MAdCAM-1 Expression, NKX2.3 Knock-Out, Spleen Anatomy, T and B Lymphocytes, Animals, Mice
Source:	EMBO Journal
ISSN:	0261-4189
Publisher:	Oxford University Press
Volume:	19
Number:	9
Page Range:	2015-2023
Date:	1 January 2000
Official Publication:	https://doi.org/10.1093/emboj/19.9.2015
PubMed:	View item in PubMed

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