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CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia

1
Department of Women, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
2
Department of Haematology, Bambino Gesù Hospital, 00165 Rome, Italy
3
Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(5), 1049; https://doi.org/10.3390/ijms20051049
Received: 21 December 2018 / Revised: 21 February 2019 / Accepted: 22 February 2019 / Published: 28 February 2019
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Abstract

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated platelet destruction, with a complex and unclear pathogenesis. The impaired immunosuppressive capacity of mesenchymal stromal cells in ITP patients (ITP-MSCs) might play a role in the development of the disease. Correcting the MSC defects could represent an alternative therapeutic approach for ITP. High-dose dexamethasone (HD-Dexa) is the mainstay of the ITP therapeutic regimen, although it has several side effects. We previously demonstrated a role for cannabinoid receptor 2 (CB2) as a mediator of anti-inflammatory and immunoregulatory properties of human MSCs. We analyzed the effects of CB2 stimulation, with the selective agonist JWH-133, and of Dexa alone and in combination on ITP-MSC survival and immunosuppressive capacity. We provided new insights into the pathogenesis of ITP, suggesting CB2 receptor involvement in the impairment of ITP-MSC function and confirming MSCs as responsive cellular targets of Dexa. Moreover, we demonstrated that CB2 stimulation and Dexa attenuate apoptosis, via Bcl2 signaling, and restore the immune-modulatory properties of MSCs derived from ITP patients. These data suggest the possibility of using Dexa in combination with JWH-133 in ITP, reducing its dose and side effects but maintaining its therapeutic benefits. View Full-Text
Keywords: immune thrombocytopenia; mesenchymal stromal cells; cannabinoid receptor 2; dexamethasone immune thrombocytopenia; mesenchymal stromal cells; cannabinoid receptor 2; dexamethasone
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Rossi, F.; Tortora, C.; Palumbo, G.; Punzo, F.; Argenziano, M.; Casale, M.; Di Paola, A.; Locatelli, F.; Perrotta, S. CB2 Receptor Stimulation and Dexamethasone Restore the Anti-Inflammatory and Immune-Regulatory Properties of Mesenchymal Stromal Cells of Children with Immune Thrombocytopenia. Int. J. Mol. Sci. 2019, 20, 1049.

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