title: NKX2.3 is required for MAdCAM-1 expression and homing of lymphocytes in spleen and mucosa-associated lymphoid tissue.
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.
authors.affiliation: Department of Cell and Molecular Biology, Institute for Biochemistry and Biotechnology, Technical University of Braunschweig, 38106 Braunschweig, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Pabst
authors.forename: R
authors.initials: R
authors.lastname: Förster
authors.forename: M
authors.initials: M
authors.lastname: Lipp
authors.forename: H
authors.initials: H
authors.lastname: Engel
authors.forename: H H
authors.initials: HH
authors.lastname: Arnold
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007136:Immunoglobulins / Q000235:genetics*; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000002:abnormalities / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009088:Mucoproteins / Q000235:genetics*; D010581:Peyer's Patches / Q000002:abnormalities / Q000166:cytology / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics; D013154:Spleen / Q000002:abnormalities / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D015533:Transcriptional Activation; D029961:Zebrafish Proteins
chemical_list: D015815:Cell Adhesion Molecules; D018398:Homeodomain Proteins; D007136:Immunoglobulins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; C102935:Nkx2.3 protein, zebrafish; D012333:RNA, Messenger; D029961:Zebrafish Proteins