Tolerogenic effect of mesenchymal stromal cells on gliadin-specific Tlymphocytes in celiac disease

Rachele Ciccocioppo, Alessandra Camarca, Giuseppina Cristina Cangemi, Giorgia Radano, Serena Vitale, Elena Betti, Davide Ferrari, Livia Visai, Elena Strada, Carla Badulli, Franco Locatelli, Catherine Klersy, Carmen Gianfrani, Gino Roberto Corazza

Research output: Contribution to journalArticlepeer-review

Abstract

Background aims: Celiac disease is caused by a dysregulated immune response toward dietary gluten, whose only treatment is a lifelong gluten-free diet. We investigated the effects of mesenchymal stromal cells (MSCs) on gliadin-specific T cells, which are known to induce intestinal lesions, in view of a possible use as new therapy. Methods: Bone marrow-derived MSCs and gliadin-specific T-cell lines were obtained from allogeneic donors and mucosal specimens of celiac patients, respectively. The immunosuppressant effect of MSCs was evaluated in terms of proliferative response and interferon (IFN)-γ production upon gliadin stimulation of long-term T-cell lines; the immunomodulant effect was assessed in terms of apoptotic rate, immunophenotype and cytokine profile of short-term T-cell lines generated in the presence of MSCs. Different MSC:T-cell ratios were applied, and statistics were performed as appropriate. Results: MSCs inhibited both proliferative response and IFN-γ production of long-term T-cell lines in a dose-dependent manner while limiting the expansion of short-term T-cell lines by increasing the apoptotic rate. Moreover, a reduction of the CD4+ population and expansion of the regulatory FoxP3+ subset were found in T-cell lines cultured with MSCs, in which a significant decrease of interleukin (IL)-21, IFN-γ and IL-10 paralleled by an upregulation of transforming growth factor-β1, IL-6 and IL-8 were observed. Finally, an increase of the indoleamine 2,3-dioxygenase activity was found, possibly playing a key role in mediating these effects. Conclusions: MSCs exert potent immunomodulant effects on gliadin-specific T cells, which may be exploited for future therapeutic application in celiac disease.

Original languageEnglish
Pages (from-to)1080-1091
Number of pages12
JournalCytotherapy
Volume16
Issue number8
DOIs
Publication statusPublished - 2014

Keywords

  • Celiac disease
  • Immune tolerance
  • Mesenchymal stromal cells
  • T lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Immunology
  • Immunology and Allergy
  • Oncology
  • Genetics(clinical)
  • Transplantation
  • Medicine(all)

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