Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis.
We have demonstrated previously that local, adenoviral-mediated gene transfer of viral IL-10 to a single joint of rabbits and mice with experimental arthritis can suppress disease in both the treated and untreated contralateral joints. This contralateral effect is mediated in part by APCs able to traffic from the treated joint to lymph nodes as well as to untreated joints. Moreover, injection of dendritic cells (DC) genetically modified to express IL-4 or Fas ligand was able to reverse established murine arthritis. To examine the ability of exosomes derived from immunosuppressive DCs to reduce inflammation and autoimmunity, murine models of delayed-type hypersensitivity and collagen-induced arthritis were used. In this study, we demonstrate that periarticular administration of exosomes purified from either bone marrow-derived DCs transduced ex vivo with an adenovirus expressing viral IL-10 or bone marrow-derived DCs treated with recombinant murine IL-10 were able to suppress delayed-type hypersensitivity responses within injected and untreated contralateral joints. In addition, the systemic injection of IL-10-treated DC-derived exosomes was able suppress the onset of murine collagen-induced arthritis as well as reduce severity of established arthritis. Taken together, these data suggest that immature DCs are able to secrete exosomes that are involved in the suppression of inflammatory and autoimmune responses. Thus DC-derived exosomes may represent a novel, cell-free therapy for the treatment of autoimmune diseases.
Kim
Seon-Hee
SH
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Lechman
Eric R
ER
Bianco
Nicole
N
Menon
Rajasree
R
Keravala
Annahita
A
Nash
Joan
J
Mi
Zhibao
Z
Watkins
Simon C
SC
Gambotto
Andrea
A
Robbins
Paul D
PD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D002458:Cell Fractionation; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000235:genetics / Q000276:immunology* / Q000637:transplantation* / Q000648:ultrastructure; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005615:Freezing; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology*; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D016753:Interleukin-10