Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis.
Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce the severity of experimental autoimmune encephalomyelitis (EAE). The mechanisms of disease suppression are dependent on regulatory T cell induction, although Tregs-independent mechanisms exist. We aimed to evaluate whether CQ is capable to modulate bone marrow-derived dendritic cells (DCs) both phenotypically and functionally as well as whether transfer of CQ-modulated DCs reduces EAE course. Our results show that CQ-treated DCs presented altered ultrastructure morphology and lower expression of molecules involved in antigen presentation. Consequently, T cell proliferation was diminished in coculture experiments. When transferred into EAE mice, DC-CQ was able to reduce the clinical manifestation of the disease through the modulation of the immune response against neuroantigens. The data presented herein indicate that chloroquine-mediated modulation of the immune system is achieved by a direct effect on DCs and that DC-CQ adoptive transfer may be a promising approach for avoiding drug toxicity.
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Rodolfo
R
Thomé
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Luidy Kazuo
LK
Issayama
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Rosaria
R
DiGangi
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Andre Luis
AL
Bombeiro
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Thiago Alves
TA
da Costa
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Isadora Tassinari
IT
Ferreira
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Alexandre Leite Rodrigues
AL
de Oliveira
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.
Liana
L
Verinaud
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D018501:Antirheumatic Agents; D002738:Chloroquine