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Altered enteroendocrine cell expression in T cell receptor alpha chain knock-out mice
1Department of Medicine, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA. drubin@im.wustl.edu
Microscopy Research and Technique
|October 31, 2000
Summary
Mice without T cell receptor alpha chains develop colon inflammation, altering specific enteroendocrine cells. This immune response impacts gut cell differentiation before epithelial damage occurs.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- T cell receptor alpha chain (TCRalpha) deficiency in mice leads to colonic inflammation.
- The impact of this inflammation on colonic epithelial cell differentiation is not fully understood.
Purpose of the Study:
- To investigate how T cell deficiency-induced colonic inflammation affects enteroendocrine cell differentiation.
- To determine if these changes occur before or after epithelial barrier disruption.
Main Methods:
- Immunohistochemistry was used to compare colonic tissues from normal C57/BL6 mice and TCR alpha(-/-) mice of different ages (2-3 weeks and 3-11 months).
- Expression levels of immune cell markers (CD45, CD4+, CD8+, B220+, IgA+) and specific enteroendocrine cell markers (cholecystokinin, serotonin, neurotensin, PYY, GLP-1, gastrin) were analyzed.
Main Results:
- TCR alpha(-/-) mice aged 3-11 months exhibited significant colonic inflammation with altered immune cell populations (increased CD45, CD4+, CD8+, B220+; decreased IgA+).
- A subset of enteroendocrine cells (cholecystokinin, serotonin, neurotensin) was significantly reduced in the colons of inflamed TCR alpha(-/-) mice.
- These specific changes in enteroendocrine cells were not observed in younger mice or in the small intestine, and the colonic epithelium remained histologically intact.
Conclusions:
- The absence of functional T cells and resulting colonic inflammation specifically impacts the differentiation of certain enteroendocrine cell populations.
- These alterations in enteroendocrine cell differentiation precede any observable loss of epithelial integrity, suggesting an early role for T cells in regulating gut endocrine function.