NKX2.3 is required for MAdCAM-1 expression and homing of lymphocytes in spleen and mucosa-associated lymphoid tissue.
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.
Pabst
O
O
Department of Cell and Molecular Biology, Institute for Biochemistry and Biotechnology, Technical University of Braunschweig, 38106 Braunschweig, Germany.
Förster
R
R
Lipp
M
M
Engel
H
H
Arnold
H H
HH
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
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