Effective treatment of inflammatory disease models with exosomes derived from dendritic cells genetically modified to express IL-4

Hee Kim Seon, Nicole R. Bianco, William J. Shufesky, Adrian E. Morelli, Paul D. Robbins

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

In this study, we demonstrate that genetically modified bone marrow-derived dendritic cells (DC) and exosomes derived from the DC, expressing either secreted IL-4 or membrane-bound IL-4, can reduce the severity and the incidence of established collagen-induced arthritis and inhibit inflammation of delayed-type hypersensitivity (DTH) in mice. The ability of the DC and DC-derived exosomes to suppress the DTH response was MHC class II and, in part, Fas ligand/Fas dependent. The DC-derived exosomes were internalized by CD11c+ DC in the dermis at the site of injection and in the draining lymph node as well as by CD11c+ DC and F4/80+ macrophages in the spleen. Moreover, adoptive transfer of CD11c+ or CD3 + splenic cells from mice treated with exosomes showed significant reduction of footpad swelling in the DTH model. These results demonstrate that administration of DC/IL-4 or exosomes derived from DC/IL-4 are able to modulate the activity of APC and T cells in vivo through a MHC class II and partly Fas ligand/Fas-dependent mechanism, resulting in effective treatment of established collagen-induced arthritis and suppression of the DTH inflammatory response. Thus, APC-derived exosomes could be used therapeutically for the treatment of autoimmune disease and inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)2242-2249
Number of pages8
JournalJournal of Immunology
Volume179
Issue number4
DOIs
StatePublished - Aug 15 2007
Externally publishedYes

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