Immunomodulatory Effects of MSC-Derived ExtracellularVesicles in Celiac Disease
8 affiliations
- 1Gastroenterology & Endoscopy Unit, Department of Medicine and Aging Sciences, Ospedale Clinicizzato SS. Annunziata, Gabriele d’Annunzio University, 66100 Chieti, Italy
- 2Institute of Biochemistry and Cell Biology, CNR, 80131 Naples, Italy
- 3European Laboratory for the Investigation of Food Induced Diseases (ELFID), 80131 Naples, Italy
- 4Haematology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi, University of Verona, 37134 Verona, Italy
- 5Hematology and Bone Marrow Transplant Unit, Section of Biomedicine of Innovation, Department of Engineering for Innovative Medicine, University of Verona, 37134 Verona, Italy
- 6Institute of Food Sciences, CNR, 83100 Avellino, Italy
- 7Institute of Genetics and Biophysics, CNR, 80131 Naples, Italy
- 8Gastroenterology Unit, San G. Moscati Hospital, 83100 Avellino, Italy
Abstract
Coeliac disease (CeD) is the most frequent chronic enteropathy, in which intestinal lesions are caused by a dysregulated immune response to gluten proteins. We aimed to investigate whether extracellular vesicles (EVs) from mesenchymal stem cells (MSC) exert immunomodulatory effects in experimental models of CeD and are potentially useful to treat CeD. A population of MSCs was obtained from bone marrow blood of adult healthy donors. EVs were purified by ultracentrifugation of MSC-supernatants and characterized in terms of size, protein content and expression of surface markers. The immunomodulatory effects of MSC-EVs were evaluated in vitro on gliadin-specific T-cell lines by detection of interferon (IFN)-γ production and ex vivo by using duodenal mucosa biopsies by measuring lymphocyte infiltration (CD3 and CD25 positive cells), IFN-γ and interleukin (IL)-10 secretion. Moreover, the MSC-EVs effects on B-cells in terms of HLA-DQ/DR and CD83/CD86 expression upon antigen stimulation was also evaluated. EVs obtained from non-celiac adult fibroblasts were used as controls. A significant and dose-dependent reduction of IFN-γ production by T cells in response to gliadin stimulation was observed in the presence of MSC-EVs (p < 0.05), but not with fibroblast-EVs. No modification of the expression of HLA class II molecules and costimulatory CD83 and CD86 markers on B cells upon EV-MSC incubation was found at any tested dose. Moreover, EVs from both MSCs and fibroblasts inhibited the gliadin-induced expansion of CD3+ and CD25+ T cells in organ cultures (p < 0.05), while increasing the IL-10 production (p < 0.05) and reducing IFN-γ (p = n.s) in organ supernatants. MSC- EVs modulated selected components of the immune response to gliadin in experimental models of CeD, including antigen-induced IFN-γ production and cellular responses in intestinal organ cultures. The effects observed in organ cultures were not exclusive to MSC-EVs, as EVs from fibroblast also modulated cellular responses. These findings provide a rationale for further preclinical investigation of EV-mediated immunomodulation in CeD.
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BibTeX
@article{ciccocioppo2026immunomodulatory,
title = {{Immunomodulatory Effects of MSC-Derived ExtracellularVesicles in Celiac Disease}},
author = {Rachele Ciccocioppo and Ilaria Mottola and Valeria Zuliani and Annalisa Adamo and Serena Vitale and Mauro Krampera and Alessandra Camarca and Vera Rotondi Aufiero and Laura Pisapia and Fabiana Capuano and Giuseppe Mazzarella and Giovanna Del Pozzo and Carmen Gianfrani},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209249},
url = {https://www.mdpi.com/1422-0067/27/20/9249},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immunomodulatory Effects of MSC-Derived ExtracellularVesicles in Celiac Disease
AU - Rachele Ciccocioppo
AU - Ilaria Mottola
AU - Valeria Zuliani
AU - Annalisa Adamo
AU - Serena Vitale
AU - Mauro Krampera
AU - Alessandra Camarca
AU - Vera Rotondi Aufiero
AU - Laura Pisapia
AU - Fabiana Capuano
AU - Giuseppe Mazzarella
AU - Giovanna Del Pozzo
AU - Carmen Gianfrani
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209249
UR - https://www.mdpi.com/1422-0067/27/20/9249
AB - Coeliac disease (CeD) is the most frequent chronic enteropathy, in which intestinal lesions are caused by a dysregulated immune response to gluten proteins. We aimed to investigate whether extracellular vesicles (EVs) from mesenchymal stem cells (MSC) exert immunomodulatory effects in experimental models of CeD and are potentially useful to treat CeD. A population of MSCs was obtained from bone marrow blood of adult healthy donors. EVs were purified by ultracentrifugation of MSC-supernatants and characterized in terms of size, protein content and expression of surface markers. The immunomodulatory effects of MSC-EVs were evaluated in vitro on gliadin-specific T-cell lines by detection of interferon (IFN)-γ production and ex vivo by using duodenal mucosa biopsies by measuring lymphocyte infiltration (CD3 and CD25 positive cells), IFN-γ and interleukin (IL)-10 secretion. Moreover, the MSC-EVs effects on B-cells in terms of HLA-DQ/DR and CD83/CD86 expression upon antigen stimulation was also evaluated. EVs obtained from non-celiac adult fibroblasts were used as controls. A significant and dose-dependent reduction of IFN-γ production by T cells in response to gliadin stimulation was observed in the presence of MSC-EVs (p < 0.05), but not with fibroblast-EVs. No modification of the expression of HLA class II molecules and costimulatory CD83 and CD86 markers on B cells upon EV-MSC incubation was found at any tested dose. Moreover, EVs from both MSCs and fibroblasts inhibited the gliadin-induced expansion of CD3+ and CD25+ T cells in organ cultures (p < 0.05), while increasing the IL-10 production (p < 0.05) and reducing IFN-γ (p = n.s) in organ supernatants. MSC- EVs modulated selected components of the immune response to gliadin in experimental models of CeD, including antigen-induced IFN-γ production and cellular responses in intestinal organ cultures. The effects observed in organ cultures were not exclusive to MSC-EVs, as EVs from fibroblast also modulated cellular responses. These findings provide a rationale for further preclinical investigation of EV-mediated immunomodulation in CeD.
SN - 1422-0067
ER -