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2016-09-01

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cc-by-nc-nd (c) AGA Institute, 2016
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/222122

Commensal-Specific CD4(+) Cells From Patients With Crohn's Disease Have a T-Helper 17 Inflammatory Profile

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https://doi.org/10.1053/j.gastro.2016.05.050

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BACKGROUND & AIMS: Crohn's disease (CD) has been associated with an altered immune response to commensal microbiota, mostly based on increased seroreactivity to microbial proteins. Although T cells are believed to contribute to the development of CD, little is known about the antigens involved. We investigated the antigen-specificity of T cells isolated from patients with CD. METHODS: We isolated peripheral blood mononuclear cells from 65 patients with CD and 45 healthy individuals (controls). We investigated T-cell reactivity to commensal microbial antigens using proliferation assays (based on thymidine incorporation and carboxyfluorescein succinimidyl ester dilution). Gene expression patterns were determined using microarray and real-time polymerase chain reaction analyses. Cytokines, chemokines, and antibodies were measured by enzyme-linked immunosorbent assay, flow cytometry, or multiplex cytokine assays. Intestinal crypts were obtained from surgical resection specimens of 7 individuals without inflammatory bowel disease. We examined the effects of commensal-specific CD4(+) T cells on primary intestinal epithelial cells from these samples. RESULTS: The bacterial proteins FlaX, A4-fla2, and YidX increased proliferation of CD4(+) T cells isolated from peripheral blood of patients with CD compared with controls. In blood samples from controls, CD4(+) T cells specific for FlaX, A4-fla2, or YidX had a T-helper (Th) 1 phenotype; a larger proportion of CD4(+) T cells specific for these proteins in patients with CD had a Th17 phenotype or produced Th1 and Th17 cytokines. When supernatants collected from commensal-specific CD4(+) T cells from patients with CD were applied to healthy intestinal epithelial cells, the epithelial cells increased the expression of the chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL8 and the CC chemokine ligand 20 (CCL20). CONCLUSIONS: A larger proportion of commensal-specific CD4(+) T cells from patients with CD have a Th17 phenotype or produce Th1 and Th17 cytokines, compared with T cells from controls; this might contribute to intestinal inflammation in patients with CD. These cells might be targeted for treatment of CD. The transcriptional data of commensal-specific CD4(+) T cells from healthy individuals and CD patients have been deposited in the Gene Expression Omnibus at the National Center for Biotechnology Information (accession no: GSE70469).

Matèries

Cèl·lules T, Antígens, Malaltia de Crohn, Resposta immunitària, Malalties inflamatòries intestinals

Matèries (anglès)

T cells, Antigens, Crohn's disease, Immune response, Inflammatory bowel diseases

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CALDERÓN GÓMEZ, Elisabeth, BASSOLAS MOLINA, Helena, MORA BUCH, Rut, DOTTI, Isabella, PLANELL PICOLA, Núria, ESTELLER VIÑAL, Miriam, GALLEGO BARRERO, Marta, MARTÍ RIPOLL, Maria mercè, GARCIA MARTIN, Carme, MARTÍNEZ TORRO, Carlos, ORDAS, Ingrid, SINGH, Sharat, PANES, Julian, BENÍTEZ-RIBAS, Daniel, SALAS MARTÍNEZ, Azucena. Commensal-Specific CD4(+) Cells From Patients With Crohn's Disease Have a T-Helper 17 Inflammatory Profile. _Gastroenterology_. 2016. Vol. 151, núm. 3, pàgs. 489. [consulta: 21 de gener de 2026]. ISSN: 0016-5085. [Disponible a: https://hdl.handle.net/2445/222122]

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