Calderón Gómez, ElisabethBassolas Molina, HelenaMora Buch, RutDotti, IsabellaPlanell Picola, NúriaEsteller Viñal, MiriamGallego Barrero, MartaMartí Ripoll, Maria MercèGarcia Martin, CarmeMartínez Torro, CarlosOrdas, IngridSingh, SharatPanes, JulianBenítez-Ribas, DanielSalas Martínez, Azucena2025-07-092025-07-092016-09-010016-5085https://hdl.handle.net/2445/222122BACKGROUND & 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).15 p.application/pdfengcc-by-nc-nd (c) AGA Institute, 2016http://creativecommons.org/licenses/by-nc-nd/4.0/Cèl·lules TAntígensMalaltia de CrohnResposta immunitàriaMalalties inflamatòries intestinalsT cellsAntigensCrohn's diseaseImmune responseInflammatory bowel diseasesinfo:eu-repo/semantics/article6768702025-07-09info:eu-repo/semantics/openAccess