Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera
Details
Publication Year 2000-08-15, Volume 224, Issue #2, Page 152-167
Journal Title
DEVELOPMENTAL BIOLOGY
Publication Type
Journal Article
Abstract
Regulated emigration of blood-borne leukocytes plays a defining role in lymphoid organ development, immune surveillance, and inflammatory responses. We report here that mice deficient in the homeobox gene Nkx2-3, expressed in developing visceral mesoderm, show a complex: intestinal malabsorption phenotype and striking abnormalities of gut-associated lymphoid tissue and spleen suggestive of deranged leukocyte homing. Mutant Peyer's patches were reduced in number and size, intestinal villi contained few IgA(+) plasma cells, and mutant spleens were small and often atrophic, showing fused periarterial lymphoid sheaths, partially merged T and B cell zones, an absent marginal zone, and a dearth of macrophages in red pulp. Semiquantitative RT-PCR analysis and immunohistochemistry revealed down-regulation of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in endothelial cells in which Nkx2-3 is normally expressed. MAdCAM-1 is a member of the immunoglobulin superfamily, acting as an endothelial cell ligand for leukocyte homing receptors L-selectin and alpha 4 beta 7 integrin. Our data suggest a role for a homeodomain factor in establishing the developmental and positional cues in endothelia that regulate leukocyte homing through local control of cellular adhesion and identify MAdCAM-1 as a candidate target gene of Nkx2-3. (C) 2000 Academic Press.
Publisher
ACADEMIC PRESS INC
Keywords
TUMOR-NECROSIS-FACTOR; FOLLICULAR DENDRITIC CELLS; TINMAN-RELATED GENES; MUCOSAL VASCULAR ADDRESSIN; LYMPHOID ORGAN DEVELOPMENT; FULL ANTIBODY-RESPONSES; ADHESION MOLECULE-1; HEART DEVELOPMENT; HOMEOBOX GENES; PEYERS-PATCHES
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Creation Date: 2000-08-15 12:00:00
Last Modified: 0001-01-01 12:00:00
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