The critical role of interleukin 4 but not interferon gamma in the pathogenesis of colitis in T-cell receptor α mutant mice
A Mizoguchi, E Mizoguchi, AK Bhan - Gastroenterology, 1999 - Elsevier
A Mizoguchi, E Mizoguchi, AK Bhan
Gastroenterology, 1999•ElsevierBackground & Aims: T-cell receptor α mutant (TCRα−/−) mice spontaneously develop colitis
resembling ulcerative colitis (UC). The role of interleukin (IL)-4 and interferon (IFN)-γ in the
pathogenesis of colitis was examined by creating IL-4–or IFN-γ–deficient TCRα−/− mice.
Methods: Double-mutant mice were created by crossing TCRα−/− mice with IL-4–or IFN-γ–
deficient mice. Colitis was grossly and histologically assessed at 6 months of age, and the
cytokine profile in the mesenteric lymph nodes and colons in these mice was analyzed …
resembling ulcerative colitis (UC). The role of interleukin (IL)-4 and interferon (IFN)-γ in the
pathogenesis of colitis was examined by creating IL-4–or IFN-γ–deficient TCRα−/− mice.
Methods: Double-mutant mice were created by crossing TCRα−/− mice with IL-4–or IFN-γ–
deficient mice. Colitis was grossly and histologically assessed at 6 months of age, and the
cytokine profile in the mesenteric lymph nodes and colons in these mice was analyzed …
Background & Aims
T-cell receptor α mutant (TCRα−/−) mice spontaneously develop colitis resembling ulcerative colitis (UC). The role of interleukin (IL)-4 and interferon (IFN)-γ in the pathogenesis of colitis was examined by creating IL-4– or IFN-γ–deficient TCRα−/− mice.
Methods
Double-mutant mice were created by crossing TCRα−/− mice with IL-4– or IFN-γ–deficient mice. Colitis was grossly and histologically assessed at 6 months of age, and the cytokine profile in the mesenteric lymph nodes and colons in these mice was analyzed.
Results
The lack of IL-4 dramatically suppressed the development of colitis at 6 months of age. In contrast, IFN-γ−/− × TCRα−/− mice developed colitis similar to that present in TCRα−/− mice. Furthermore, proliferation of colonic epithelial cells was markedly increased in TCRα−/− mice and IFN-γ−/− × TCRα−/− mice compared with IL-4−/− × TCRα−/− mice. Continuous administration of recombinant IL-4 led to increased colonic epithelial cell proliferation in IL-4−/− × TCRα−/− mice.
Conclusions
IL-4 plays an important role in the development of colitis in TCRα−/− mice. In contrast, severe colitis in TCRα−/− mice can develop in the absence of IFN-γ. GASTROENTEROLOGY 1999;116:320-326
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