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Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia
- Source :
- Proceedings of the National Academy of Sciences. 101:16016-16021
- Publication Year :
- 2004
- Publisher :
- Proceedings of the National Academy of Sciences, 2004.
-
Abstract
- RUNX transcription factors are key regulators of lineage-specific gene expression and might be involved in autoimmune diseases. Runx3 plays a role during the development of sensory neurons and T cells and regulates transforming growth factor β (TGF-β) signaling in dendritic cells. Here, we report that at 4 weeks of age, Runx3 knockout (KO) mice spontaneously develop inflammatory bowel disease (IBD) characterized by leukocyte infiltration, mucosal hyperplasia, formation of lymphoid clusters, and increased production of IgA. Additionally, at a considerably older age (8 months), the KO mice also develop progressive hyperplasia of the gastric mucosa associated with disturbed epithelial differentiation and cellular hyaline degeneration. Analysis of cytokines in the colonic mucosa of Runx3 KO mice revealed a mixed T helper 1/T helper 2 response. By using immunohistochemistry and RNAin situhybridization, Runx3 expression in the gastrointestinal tract is detected in lymphoid and myeloid populations but not in the epithelium. The data indicate that loss of leukocytic cell-autonomous function of Runx3 results in IBD and gastric lesion in the KO mice. IBD in humans is viewed as a complex genetic disorder. Several susceptibility loci were identified on different human chromosomes including the chromosomal region 1p36 whereRUNX3resides. It is thus tempting to speculate that mutations inRUNX3may constitute an IBD risk factor in humans.
- Subjects :
- Myeloid
In situ hybridization
Biology
Inflammatory bowel disease
Mice
Th2 Cells
Leukocytes
medicine
Gastric mucosa
Animals
Humans
Colitis
In Situ Hybridization
Mice, Knockout
Mice, Inbred BALB C
Hyperplasia
Multidisciplinary
Th1 Cells
Biological Sciences
Inflammatory Bowel Diseases
medicine.disease
Immunohistochemistry
digestive system diseases
DNA-Binding Proteins
Mice, Inbred C57BL
Core Binding Factor Alpha 3 Subunit
medicine.anatomical_structure
Gastric Mucosa
Immunology
Chromosomal region
Cytokines
Transcription Factors
Transforming growth factor
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 101
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....421d24d608d81f15965cc826e8c22b00