期刊
GASTROENTEROLOGY
卷 138, 期 1, 页码 275-284出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2009.09.016
关键词
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资金
- NIH [DK071576, AI044236]
- EPA [R834064]
- Food Allergy Initiative
- Crohn's and Colitis Foundation of America
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI044236, U19AI044236] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R21DK071576] Funding Source: NIH RePORTER
BACKGROUND & AIMS: CCL20 is a chemokine that regulates the homeostatic and inflammatory trafficking of leukocytes to the small intestine and regulates the development OF the gastrointestinal lymphoid architecture. T cells expressing T helper cell (Th)2 cytokines are critical for experimental food allergy, and we hypothesized that CCL20 is involved in the localization of these cells to the gut. METHODS: We evaluated the role of CCR6 in allergic diarrhea induced by sensitization and oral challenge with ovalbumin (OVA) using CCR6(+/+) and CCR6(-/-) mice. RESULTS: CCR6(-/-) mice were protected from OVA-induced diarrhea but surprisingly were not impaired in mastocytosis or allergen-specific immunoglobulin E. CCR6(-/-) mice were also protected from T cell-mediated diarrhea induced by anti-CD3 antibody. Allergic diarrhea was associated with an increased expression of Th2 cytokines within the intestinal mucosa that was significantly reduced in CCR6(-/-) mice. Inhibition OF lymphocyte homing by treatment with FTY720 did not impair allergic diarrhea, indicating that reactivation of T cells Could Occur locally within the small intestine. Finally, T-cell transfer studies demonstrated that CCR6 was required both on the transferred T cells and in the recipient Mouse to manifest allergic disease in the gastrointestinal tract. CONCLUSIONS: These studies highlight a mast cell- and immunoglobulin E-independent role for CCR6-bearing T cells in the pathogenesis of gastrointestinal allergic disease.
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