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NKX2.3 is required for MAdCAM‐1 expression and homing of lymphocytes in spleen and mucosa‐associated lymphoid tissue
Author(s) -
Pabst Oliver,
Förster Reinhold,
Lipp Martin,
Engel Holger,
Arnold HansHenning
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.9.2015
Subject(s) - addressin , biology , spleen , homing (biology) , mesenteric lymph nodes , marginal zone , lymphatic system , cell adhesion molecule , lymphocyte homing receptor , immunology , cell adhesion , microbiology and biotechnology , b cell , cell , antibody , genetics , ecology
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.