Topical application of soluble CD83 induces IDO-mediated immune modulation, increases Foxp3+ T cells, and prolongs allogeneic corneal graft survival
Bock F, Roessner S, Onderka J, Lechmann M, Pallotta MT, Fallarino F, Boon L, Nicolette C, Debenedette MA, Tcherepanova IY, Grohmann U, Steinkasserer A, Cursiefen C, Zinser E (2013)
Publication Type: Journal article
Publication year: 2013
Journal
Book Volume: 191
Pages Range: 1965-75
Journal Issue: 4
Abstract
Modulation of immune responses is one of the main research aims in transplant immunology. In this study, we investigate the local immunomodulatory properties of soluble CD83 (sCD83) at the graft-host interface using the high-risk corneal transplantation model. In this model, which mimics the inflammatory status and the preexisting vascularization of high-risk patients undergoing corneal transplantation, allogeneic donor corneas are transplanted onto sCD83-treated recipient animals. This model allows the direct and precise application of the immune modulator at the transplantation side. Interestingly, sCD83 was able to prolong graft survival after systemic application as well as after topical application, which is therapeutically more relevant. The therapeutic effect was accompanied by an increase in the frequency of regulatory T cells and was mediated by the immune-regulatory enzyme IDO and TGF-?. In vitro, sCD83 induced long-term IDO expression in both conventional and plasmacytoid dendritic cells via autocrine or paracrine production of TGF-?, a cytokine previously shown to be an essential mediator of IDO-dependent, long-term tolerance. These findings open new treatment avenues for local immune modulation after organ and tissue transplantation.
Authors with CRIS profile
Matthias Lechmann
Department of Immune Modulation
Alexander Steinkasserer
Professur für Experimentelle Dermatologie
Involved external institutions
Bioceros Holding B.V.
Netherlands (NL)
Argos Therapeutics, Inc.
United States (USA) (US)
Università degli Studi di Perugia
Italy (IT)
Universität zu Köln
Germany (DE)
Netherlands (NL)
Argos Therapeutics, Inc.
United States (USA) (US)
Università degli Studi di Perugia
Italy (IT)
Universität zu Köln
Germany (DE)
How to cite
APA:
Bock, F., Roessner, S., Onderka, J., Lechmann, M., Pallotta, M.T., Fallarino, F.,... Zinser, E. (2013). Topical application of soluble CD83 induces IDO-mediated immune modulation, increases Foxp3+ T cells, and prolongs allogeneic corneal graft survival. Journal of Immunology, 191(4), 1965-75. https://doi.org/10.4049/jimmunol.1201531
MLA:
Bock, Felix, et al. "Topical application of soluble CD83 induces IDO-mediated immune modulation, increases Foxp3+ T cells, and prolongs allogeneic corneal graft survival." Journal of Immunology 191.4 (2013): 1965-75.
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