HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0804186v1 183/10/6058    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Peng, Q. Articles by Zhou, W. PubMed PubMed Citation Articles by Peng, Q. Articles by Zhou, W.

Dendritic Cell Function in Allostimulation Is Modulated by C5aR Signaling¹

Qi Peng,^* Ke Li,^* Naiyin Wang,^* Qijun Li,^* Elham Asgari,^* Bao Lu, Trent M. Woodruff, Steven H. Sacks,^* and Wuding Zhou^2*

^*Complement Laboratory, MRC Centre for Transplantation, King’s College London, School of Medicine at Guy’s Hospital, London, U.K.; Division of Pulmonary Medicine and Ina Sue Perlmutter Laboratory, Children’s Hospital, Harvard Medical School, Boston, MA 02115; and School of Biomedical Sciences, University of Queensland, Brisbane, Australia

Regulation of T cell immunity by C5a has been suggested from recent studies. However, the underlying mechanisms, particularly the involved cells and biochemical basis, are not well defined. In this study, the direct modulation of dendritic cell (DC) activation and its function in T cell stimulation by C5a-C5aR interaction and the involved signaling pathways were investigated. We show that DCs from C5aR^–/– mice and normal DCs treated with C5aR antagonist have less-activated phenotype characterized with increased IL-10 and decreased IL-12p70 production in response to LPS stimulation, lowered surface expression of MHC class II, B7.2, and consequently have reduced capacity to stimulate allospecific T cells. Conversely, C5a stimulation up-regulates DC activation and its function in allostimulation. Furthermore, stimulation of C5aR mediates the inhibition of cAMP production and protein kinase A activity and is involved in activation of PI3K/AKT and NF-B signaling in DCs. These results demonstrate that C5a acts directly on C5aR expressed on DCs resulting in the cell activation and subsequently enhances its capacity for allospecific T cell stimulation. It also suggests that NF-B signaling induced by down-regulation of cAMP/ protein kinase A pathway and up-regulation of PI3K/AKT pathway following C5a stimulation may contribute to up-regulation of DC function.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Medical Research Council of the U.K.

² Address correspondence and reprint requests to: Dr. Wuding Zhou, Complement Laboratory, MRC Centre for Transplantation, King’s College London, 5^th Floor Tower Wing, Guy’s Hospital, Great Maze Pond, London, U.K. E-mail: wuding.zhou{at}kcl.ac.uk

³ Abbreviations used in this paper: DC, dendritic cell; PKA, protein kinase A; C5aRa, C5aR antagonist; WT, wild-type; BM, bone marrow; qRT-PCR, quantitative RT-PCR; PKA, protein kinase A; p-PKA, phosphorylated PKA.

⁴ The online version of this article contains supplementary material.