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

Elisabeth Calderón-Gómez, Helena Bassolas-Molina, Rut Mora-Buch, Isabella Dotti, Núria Planell, Míriam Esteller, Marta Gallego, Mercè Martí, Carme Garcia-Martín, Carlos Martínez-Torró, Ingrid Ordás, Sharat Singh, Julian Panés, Daniel Benítez-Ribas, Azucena Salas

Research output: Contribution to journalArticleResearchpeer-review

40 Citations (Scopus)

Abstract

© 2016 AGA Institute 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).
Original languageEnglish
Pages (from-to)489-500.e3
JournalGastroenterology
Volume151
Issue number3
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • Antigen-Specific Immune Response
  • Effector T Cells
  • IBD
  • Immunity

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