أعرض في EDS

Role of β7 Integrin and the Chemokine/Chemokine Receptor Pair CCL25/CCR9 in Modeled TNF-Dependent Crohn's Disease

التفاصيل البيبلوغرافية
العنوان: Role of β7 Integrin and the Chemokine/Chemokine Receptor Pair CCL25/CCR9 in Modeled TNF-Dependent Crohn's Disease
المؤلفون: Konstantinos A. Papadakis, Werner Müller, Maria Apostolaki, Manolis Roulis, Marc–André Wurbel, George Kollias, Menelaos Manoloukos, Bernard Malissen, Dimitris L. Kontoyiannis
المساهمون: Institute of Immunology, Alexander Fleming Center, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
المصدر: Gastroenterology
Gastroenterology, WB Saunders, 2008, 134 (7), pp.2025-35. ⟨10.1053/j.gastro.2008.02.085⟩
Gastroenterology, 2008, 134 (7), pp.2025-35. ⟨10.1053/j.gastro.2008.02.085⟩
بيانات النشر: Elsevier BV, 2008.
سنة النشر: 2008
مصطلحات موضوعية: Integrins, Chemokine, Integrin beta Chains, Time Factors, medicine.medical_treatment, MESH: Chemotaxis, Leukocyte, CCR9, MESH: Flow Cytometry, CD8-Positive T-Lymphocytes, MESH: Mice, Knockout, Mice, Chemokine receptor, MESH: Receptors, CCR, 0302 clinical medicine, Crohn Disease, MESH: Integrin beta Chains, MESH: Animals, Mice, Knockout, 0303 health sciences, Gastroenterology, MESH: Integrins, T-Lymphocytes, Helper-Inducer, T helper cell, Flow Cytometry, MESH: CD8-Positive T-Lymphocytes, Intestinal epithelium, MESH: Chemokines, CC, Chemotaxis, Leukocyte, medicine.anatomical_structure, Cytokine, Chemokines, CC, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030211 gastroenterology & hepatology, Colon, MESH: Interferon Type II, MESH: Mice, Transgenic, CD8 Antigens, Mice, Transgenic, Biology, Interferon-gamma, Receptors, CCR, 03 medical and health sciences, MESH: Mice, Inbred C57BL, medicine, Animals, MESH: T-Lymphocytes, Helper-Inducer, MESH: Colon, MESH: Mice, 030304 developmental biology, MESH: Crohn Disease, Hepatology, Tumor Necrosis Factor-alpha, MESH: Time Factors, Mice, Inbred C57BL, Disease Models, Animal, MESH: Tumor Necrosis Factor-alpha, Immunology, biology.protein, Cancer research, Intraepithelial lymphocyte, MESH: Antigens, CD8, MESH: Disease Models, Animal, CCL25
الوصف: International audience; BACKGROUND & AIMS: In the present work, we address the requirement for intestinal-specific homing molecules, the chemokine/chemokine receptor pair CCL25/CCR9 and beta7 integrin, in the pathogenesis of the CD8(+) T cell-dependent Tnf(DeltaARE) 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, alpha4beta7, and alphaEbeta7 integrin. The functional significance of CCL25/CCR9 and beta7 integrin in inflammatory lymphocyte recruitment and intestinal disease development was assessed in Tnf(DeltaARE) mice genetically lacking these molecules. RESULTS: Intestinal inflammation in the Tnf(DeltaARE) mice is associated with early reduction of CD8alphaalpha-expressing intraepithelial lymphocytes, decreased T helper cell 1 and increased T helper cell 17 responses by LP CD4(+) lymphocytes, increased alphaEbeta7 integrin expression in peripheral activated/memory intestinal-homing CD8alphabeta lymphocytes, and predominance of tumor necrosis factor/interferon-gamma-producing CD8alphabeta 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, CD8alphabeta lymphocyte recruitment in the intestinal epithelium and inflammatory infiltration in the LP are not impaired in CCR9- or CCL25-deficient Tnf(DeltaARE) mice. In contrast, genetic ablation of beta7 integrin results in complete amelioration of intestinal pathology. CONCLUSIONS: Our findings demonstrate that development of intestinal inflammation in the Tnf(DeltaARE) mice is critically dependent on beta7 integrin-mediated T-lymphocyte recruitment, whereas the function of the CCL25/CCR9 axis appears dispensable in this model.
تدمد: 0016-5085
1528-0012
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ccde4e10e5d5180a1f3aeb9538627584
https://doi.org/10.1053/j.gastro.2008.02.085
حقوق: CLOSED
رقم الأكسشن: edsair.doi.dedup.....ccde4e10e5d5180a1f3aeb9538627584
قاعدة البيانات: OpenAIRE
الوصف
تدمد:00165085
15280012