Frontiers in Immunology (Jun 2018)
Prostaglandin E2 Stimulates the Expansion of Regulatory Hematopoietic Stem and Progenitor Cells in Type 1 Diabetes
- Moufida Ben Nasr,
- Moufida Ben Nasr,
- Francesca D’Addio,
- Amir Mohammad Malvandi,
- Silvia Faravelli,
- Eduardo Castillo-Leon,
- Vera Usuelli,
- Vera Usuelli,
- Francesca Rocchio,
- Teresa Letizia,
- Abdel Basset El Essawy,
- Emma Assi,
- Chiara Mameli,
- Chiara Mameli,
- Chiara Mameli,
- Elisa Giani,
- Elisa Giani,
- Elisa Giani,
- Maddalena Macedoni,
- Anna Maestroni,
- Alice Dassano,
- Cristian Loretelli,
- Moira Paroni,
- Giuseppe Cannalire,
- Giacomo Biasucci,
- Marco Sala,
- Alessandra Biffi,
- Alessandra Biffi,
- Gian Vincenzo Zuccotti,
- Gian Vincenzo Zuccotti,
- Gian Vincenzo Zuccotti,
- Gian Vincenzo Zuccotti,
- Paolo Fiorina,
- Paolo Fiorina,
- Paolo Fiorina
Affiliations
- Moufida Ben Nasr
- Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Moufida Ben Nasr
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Francesca D’Addio
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Amir Mohammad Malvandi
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Silvia Faravelli
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Eduardo Castillo-Leon
- Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Vera Usuelli
- Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Vera Usuelli
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Francesca Rocchio
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Teresa Letizia
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Abdel Basset El Essawy
- Medicine, Al-Azhar University, Cairo, Egypt
- Emma Assi
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Chiara Mameli
- Department of Pediatrics, Buzzi Children Hospital, Milan, Italy
- Chiara Mameli
- Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Chiara Mameli
- Department of Pediatrics, Children’s Hospital Buzzi, Milan, Italy
- Elisa Giani
- Department of Pediatrics, Buzzi Children Hospital, Milan, Italy
- Elisa Giani
- Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Elisa Giani
- Department of Pediatrics, Children’s Hospital Buzzi, Milan, Italy
- Maddalena Macedoni
- Department of Pediatrics, Diabetes Service Studies, University of Milan, Ospedale dei Bambini Vittore Buzzi, Milan, Italy
- Anna Maestroni
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Alice Dassano
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Cristian Loretelli
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Moira Paroni
- Department of Bioscience, University of Milan, Milan, Italy
- Giuseppe Cannalire
- Department of Pediatrics and Neonatology, Ospedale Guglielmo da Saliceto, Piacenza, Italy
- Giacomo Biasucci
- Department of Pediatrics and Neonatology, Ospedale Guglielmo da Saliceto, Piacenza, Italy
- Marco Sala
- 0Department of Pediatrics, Tradate Hospital, Tradate, Italy
- Alessandra Biffi
- 1Gene Therapy Program, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, MA, United States
- Alessandra Biffi
- 2Harvard Medical School, Boston, MA, United States
- Gian Vincenzo Zuccotti
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Gian Vincenzo Zuccotti
- Department of Pediatrics, Buzzi Children Hospital, Milan, Italy
- Gian Vincenzo Zuccotti
- Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Gian Vincenzo Zuccotti
- Department of Pediatrics, Children’s Hospital Buzzi, Milan, Italy
- Paolo Fiorina
- Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
- Paolo Fiorina
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy
- Paolo Fiorina
- 3Division of Endocrinology, ASST Sacco Fatebenefratelli-Sacco, Milan, Italy
- DOI
- https://doi.org/10.3389/fimmu.2018.01387
- Journal volume & issue
-
Vol. 9
Abstract
Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only “experimental therapy” that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D, ex vivo modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human in vitro autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes.
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