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CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2

Author:
Chen, Liwen, Zhu, Yibei, Zhang, Guangbo, Gao, Chao, Zhong, Weixue, Zhang, Xueguang
Source:
Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.46 pp. 18778-18783
ISSN:
0027-8424
Subject:
CD4-positive T-lymphocytes, dendritic cells, immune response, interferon-gamma, monocytes, transforming growth factor beta
Abstract:
CD83 is commonly known as a specific marker for mature dendritic cells. It has been shown to be important for CD4+ T-cell development in the thymus. However, its function in the peripheral immune system remains enigmatic. Here, we show that CD83 inhibits proliferation and production of IL-2 and IFN-γ by T cells, and the inhibitory effect of CD83 is mediated by monocytes. Prostaglandin E2 (PGE2), but not IL-10 or TGF-β, was up-regulated specifically by CD83 in monocytes. Consistent with high levels of PGE2, expression of COX-2 also was increased upon CD83 treatment. NF-κB activation also is required for induction of PGE2 by CD83. Finally, application of the COX-2–selective inhibitor NS-398 fully prevented CD83-triggered inhibition of T-cell responses. Our study establishes an immune-regulatory mechanism by CD83 via stimulation of PGE2 production in monocytes.
Agid:
422343