کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3296683 | 1209872 | 2008 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Role of β7 Integrin and the Chemokine/Chemokine Receptor Pair CCL25/CCR9 in Modeled TNF-Dependent Crohn's Disease Role of β7 Integrin and the Chemokine/Chemokine Receptor Pair CCL25/CCR9 in Modeled TNF-Dependent Crohn's Disease](/preview/png/3296683.png)
Background & Aims: In the present work, we address the requirement for intestinal-specific homing molecules, the chemokine/chemokine receptor pair CCL25/CCR9 and β7 integrin, in the pathogenesis of the CD8+ T cell-dependent TnfΔARE mouse model of Crohn's-like inflammatory bowel disease. Methods: We investigated by flow cytometry lymphocyte recruitment in the intestinal epithelium and lamina propria (LP); cytokine production by intraepithelial and LP lymphocytes; and peripheral expression of CCR9, α4β7, and αEβ7 integrin. The functional significance of CCL25/CCR9 and β7 integrin in inflammatory lymphocyte recruitment and intestinal disease development was assessed in TnfΔARE mice genetically lacking these molecules. Results: Intestinal inflammation in the TnfΔARE mice is associated with early reduction of CD8αα-expressing intraepithelial lymphocytes, decreased T helper cell 1 and increased T helper cell 17 responses by LP CD4+ lymphocytes, increased αEβ7 integrin expression in peripheral activated/memory intestinal-homing CD8αβ lymphocytes, and predominance of tumor necrosis factor/interferon-γ-producing CD8αβ lymphocytes in the epithelium. Although CCL25/CCR9 have been strongly implicated in T-lymphocyte recruitment to the small intestine, inflammatory pathology develops unperturbed in the genetic absence of CCL25/CCR9. Furthermore, CD8αβ lymphocyte recruitment in the intestinal epithelium and inflammatory infiltration in the LP are not impaired in CCR9- or CCL25-deficient TnfΔARE mice. In contrast, genetic ablation of β7 integrin results in complete amelioration of intestinal pathology. Conclusions: Our findings demonstrate that development of intestinal inflammation in the TnfΔARE mice is critically dependent on β7 integrin-mediated T-lymphocyte recruitment, whereas the function of the CCL25/CCR9 axis appears dispensable in this model.
Journal: Gastroenterology - Volume 134, Issue 7, June 2008, Pages 2025–2035