Immunoregulatory effects of myeloid-derived suppressor cell exosomes in mouse model of autoimmune Alopecia Areata

• Verfasst von: Zöller, Margot [VerfasserIn]
• Verfasst von: Zhao, Kun [VerfasserIn]
• Verfasst von: Kutlu, Natalia [VerfasserIn]
• Verfasst von: Bauer, Nathalie [VerfasserIn]
• Verfasst von: Provaznik, Jan [VerfasserIn]
• Verfasst von: Hackert, Thilo [VerfasserIn]
• Verfasst von: Schnölzer, Martina [VerfasserIn]
• Titel: Immunoregulatory effects of myeloid-derived suppressor cell exosomes in mouse model of autoimmune Alopecia Areata
• Verf.angabe: Margot Zöller, Kun Zhao, Natalia Kutlu, Nathalie Bauer, Jan Provaznik, Thilo Hackert and Martina Schnölzer
• E-Jahr: 2018
• Jahr: 06 June 2018
• Fussnoten: Gesehen am 13.11.2019
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2018
• Band/Heft Quelle: 9(2018) Artikel-Nummer 1279, 21 Seiten
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2018.01279
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Alopecia Areata
• Sach-SW: Exosomes
• Sach-SW: myeloid-derived suppressor cells
• Sach-SW: regulatory T cells
• Sach-SW: therapy
• K10plus-PPN: 1681762641
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

The treatment of autoimmune diseases still poses a major challenge, frequently relying on non-specific immunosuppressive drugs. Current efforts aim at reestablishing self tolerance using immune cells with suppressive activity like the regulatory T cells (Treg) or the myeloid-derived suppressor cells (MDSC). We have demonstrated therapeutic efficacy of MDSC in mouse Alopecia Areata (AA). In the same AA model, we now asked whether MDSC exosomes (MDSC-Exo) can replace MDSC. MDSC-Exo from bone marrow cells (BMC) cultures of healthy donors could substantially facilitate treatment. With knowledge on MDSC-Exo being limited, their suitability needs to be verified in advance. Protein marker profiles suggest comparability of BMC- to ex vivo collected inflammatory MDSC/MDSC-Exo in mice with a chronic contact dermatitis, which is a therapeutic option in AA. Proteome analyses substantiated a large overlap of function-relevant molecules in MDSC and MDSC-Exo. Furthermore, MDSC-Exo are taken up by T cells, macrophages, NK and most avidly by Treg and MDSC-Exo uptake exceeds binding of MDSC themselves. In AA mice, MDSC-Exo preferentially target skin-draining lymph nodes and cells in the vicinity of remnant hair follicles. MDSC-Exo uptake is accompanied by a strong increase in Treg, reduced T helper proliferation, mitigated cytotoxic activity and a slight increase in lymphocyte apoptosis. Repeated MDSC-Exo application in florid AA prevented progression and sufficed for partial hair regrowth. Deep sequencing of lymphocyte mRNA from these mice revealed a significant increase in immunoregulatory mRNA, including FoxP3 and arginase 1. Downregulated mRNA was preferentially engaged in prohibiting T cell hyperreactivity. Taken together, proteome analysis provided important insights into potential MDSC-Exo activities, these exosomes preferentially homing into AA-affected organs. Most importantly, changes in leukocyte mRNA seen after treatment of AA mice with MDSC-Exo sustainably supports the strong impact on the adaptive and the non-adaptive immune system, with Treg expansion being a dominant feature. Thus, MDSC-Exo could potentially serve as therapeutic agents in treating AA and other autoimmune diseases.