Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera
- Author(s)
- Wang, CC; Biben, C; Robb, L; Nassir, F; Barnett, L; Davidson, NO; Koentgen, F; Tarlinton, D; Harvey, RP;
- 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
- Publisher's Version
- https://doi.org/10.1006/dbio.2000.9749
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-08-15 12:00:00