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

Official URL:https://doi.org/10.1093/emboj/19.9.2015
PubMed:View item in PubMed
Creators Name:Pabst, O. and Foerster, R. and Lipp, M. and Engel, H. and Arnold, H.H.
Journal Title:EMBO Journal
Journal Abbreviation:EMBO J
Page Range:2015-2023
Date:1 January 2000
Keywords:Lymphocyte Homing, MAdCAM-1 Expression, NKX2.3 Knock-Out, Spleen Anatomy, T and B Lymphocytes, Animals, Mice
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.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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