Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease.
There is a need in autoimmune diseases to uncover the mechanisms involved in the natural resolution of inflammation. In this article, we demonstrate that granulocytic myeloid-derived suppressor cells (G-MDSCs) abundantly accumulate within the peripheral lymphoid compartments and target organs of mice with experimental autoimmune encephalomyelitis prior to disease remission. In vivo transfer of G-MDSCs ameliorated experimental autoimmune encephalomyelitis, significantly decreased demyelination, and delayed disease onset through inhibition of encephalitogenic Th1 and Th17 immune responses. Exposure of G-MDSCs to the autoimmune milieu led to up-regulation of the programmed death 1 ligand that was required for the G-MDSC-mediated suppressive function both in vitro and in vivo. Importantly, myeloid-derived suppressor cells were enriched in the periphery of subjects with active multiple sclerosis and suppressed the activation and proliferation of autologous CD4(+) T cells ex vivo. Collectively, this study revealed a pivotal role for myeloid-derived suppressor cells in the regulation of multiple sclerosis, which could be exploited for therapeutic purposes.
Laboratory of Autoimmunity and Inflammation, University of Crete, Medical School, 71300 Heraklion, Greece.
Marianna
M
Ioannou
Themis
T
Alissafi
Iakovos
I
Lazaridis
George
G
Deraos
John
J
Matsoukas
Achille
A
Gravanis
Vasileios
V
Mastorodemos
Andreas
A
Plaitakis
Arlene
A
Sharpe
Dimitrios
D
Boumpas
Panayotis
P
Verginis
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017690:Cell Transplantation; D002493:Central Nervous System Diseases / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy; D006098:Granulocytes / Q000276:immunology*; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology