Dr. Robbins has received consulting fees, speaking fees, and/or honoraria from Tissuegene, Inc. and Orthogen (less than $10,000 each).
Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase–positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models
Article first published online: 29 JAN 2009
Copyright © 2009 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 60, Issue 2, pages 380–389, February 2009
How to Cite
Bianco, N. R., Kim, S. H., Ruffner, M. A. and Robbins, P. D. (2009), Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase–positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models. Arthritis & Rheumatism, 60: 380–389. doi: 10.1002/art.24229
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- Manuscript Accepted: 3 OCT 2008
- Manuscript Received: 9 OCT 2007
- NIH. Grant Number: AI-56374
- Juvenile Diabetes Research Foundation. Grant Number: 7-2005-1154
We have demonstrated previously that dendritic cells (DCs) modified with immunosuppressive cytokines, and exosomes derived from DCs can suppress the onset of murine collagen-induced arthritis (CIA) and reduce the severity of established arthritis. Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme that is important for immune regulation and tolerance maintenance. DCs expressing functional IDO can inhibit T cells by depleting them of essential tryptophan and/or by producing toxic metabolites, as well as by generating Treg cells. This study was undertaken to examine the immunosuppressive effects of bone marrow (BM)–derived DCs genetically modified to express IDO, and of exosomes derived from IDO-positive DCs.
BM-derived DCs were adenovirally transduced with IDO or CTLA-4Ig (an inducer of IDO), and the resulting DCs and exosomes were tested for their immunosuppressive ability in the CIA and delayed-type hypersensitivity (DTH) murine models.
Both DCs and exosomes derived from DCs overexpressing IDO had an antiinflammatory effect in CIA and DTH murine models. The suppressive effects were partially dependent on B7 costimulatory molecules. In addition, gene transfer of CTLA-4Ig to DCs resulted in induction of IDO in the DCs and in exosomes able to reduce inflammation in an IDO-dependent manner.
These results demonstrate that both IDO-expressing DCs and DC-derived exosomes are immunosuppressive and antiinflammatory, and are able to reverse established arthritis. Therefore, exosomes from IDO-positive DCs may represent a novel therapy for rheumatoid arthritis.