Title

Bone marrow-derived dendritic cells generated in the presence of resolvin E1 induce apoptosis of activated CD4+ T cells

Document Type

Article

Publication Date

10-1-2008

Abstract

In contrast to the role of dendritic cells (DC) in immunity and tolerance, little is known about their possible role in the resolution of inflammatory processes. In addition to the reduction in the number of infiltrating immune cells, the elimination of effector T cells already present at the inflammatory site represents an essential step toward resolution. Recently, lipid mediators such as the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and their metabolites, including resolvin E1 (RvE1), have been shown to accumulate in inflammatory foci during the resolution phase. RvE1 has been reported to reduce immune cell infiltration and proinflammatory cytokine production. In this study we report that DC exposed to RvE1, especially during differentiation, acquire the capacity to induce apoptosis of activated T cells through the induction and activity of indoleamine 2,3-dioxygenase. To our knowledge, this study is the first to report on an omega-3 fatty acid derivative inducing indoleamine 2,3-dioxygenase expression in DC. RvE1-exposed DC maintain an immature chemokine receptor expression pattern even following TLR stimulation, with high CCR5 and no CCR7 expression. This effect implies that DC exposed to RvE1 and pathogens remain at the inflammatory site, instead of migrating to lymph nodes, and induce apoptosis in effector T cells infiltrating the inflammatory site. To our knowledge, the DC described in this study represent a new functional DC subtype, whose essential function resides in the resolution of inflammation. Copyright © 2008 by The American Association of Immunologists, Inc.

Publication Title

Journal of Immunology

First Page Number

4534

Last Page Number

4544

DOI

10.4049/jimmunol.181.7.4534

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