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. © 2014 International Society for Cellular Therapy.

Tolerogenic effect of mesenchymal stromal cells on gliadin-specific Tlymphocytes in celiac disease / Ciccocioppo, R.; Camarca, A.; Cangemi, G. C.; Radano, G.; Vitale, S.; Betti, E.; Ferrari, D.; Visai, L.; Strada, E.; Badulli, C.; Locatelli, F.; Klersy, C.; Gianfrani, C.; Corazza, G. R.. - In: CYTOTHERAPY. - ISSN 1465-3249. - 16:8(2014), pp. 1080-1091. [10.1016/j.jcyt.2014.03.002]

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

Locatelli F.;
2014

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. © 2014 International Society for Cellular Therapy.
2014
Celiac disease; Immune tolerance; Mesenchymal stromal cells; T lymphocytes
01 Pubblicazione su rivista::01a Articolo in rivista
Tolerogenic effect of mesenchymal stromal cells on gliadin-specific Tlymphocytes in celiac disease / Ciccocioppo, R.; Camarca, A.; Cangemi, G. C.; Radano, G.; Vitale, S.; Betti, E.; Ferrari, D.; Visai, L.; Strada, E.; Badulli, C.; Locatelli, F.; Klersy, C.; Gianfrani, C.; Corazza, G. R.. - In: CYTOTHERAPY. - ISSN 1465-3249. - 16:8(2014), pp. 1080-1091. [10.1016/j.jcyt.2014.03.002]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1489599
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