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

This Article Full Text (PDF) All Versions of this Article: jimmunol.0803955v1 183/11/7398    most recent Alert me when this article is cited Alert me if a correction is posted 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 Lin, A.-f. Articles by Shao, J.-z. PubMed PubMed Citation Articles by Lin, A.-f. Articles by Shao, J.-z.

The DC-SIGN of Zebrafish: Insights into the Existence of a CD209 Homologue in a Lower Vertebrate and Its Involvement in Adaptive Immunity¹

*College of Life Sciences, Zhejiang University, Hangzhou 310058, Peoples Republic of China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou, Peoples Republic of China; and Key Laboratory of Animal Epidemic Etiology and Immunology Prevention of the Ministry of Agriculture, Hangzhou, People's Republic of China

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN/CD209) has become hot topic in recent studies because of its important roles in immune responses and immune escape. CD209 has been well characterized in humans and several other mammals, but little documentation exists about it in lower vertebrates. This is the first report on the identification and functional characterization of a fish DC-SIGN/CD209 molecule. The zebrafish DC-SIGN/CD209 cDNA translates into 343 aa organized into three domains structurally conserved among vertebrates. An EPN motif essential for interacting with Ca²⁺ and for recognizing mannose-containing motifs has been identified. Several conserved motifs crucial for internalization and signal transduction are also present within the cytoplasmic tail. Phylogenetic analysis supports the hypothesis that CD209 family members diverged from a common ancestor. The expression of DC-SIGN/CD209 in immune-related tissues can be significantly up-regulated by exogenous Ags and IL-4. This molecule associates with various APCs, including macrophages, B lymphocytes, and a possible dendritic cell-like (CD83⁺/CD80⁺CD209⁺) population. Functionally, T cell activation, Ab (IgM) production, and bacterial vaccination-elicited immunoprotection can be dramatically inhibited by a CD209 blockade after stimulation with keyhole limpet hemocyanin (KLH) in vivo or challenged with Aeromonas hydrophila, suggesting that DC-SIGN/CD209 in zebrafish is crucial for the initiation and development of adaptive immunity. Phagocytosis analysis showed that DC-SIGN/CD209 does not participate in the uptake of KLH Ag, suggesting that other mechanisms might exist that underlie DC-SIGN/CD209 involvement. We hope that the present study will contribute to a better cross-species understanding of the evolutionary history of the DC-SIGN/CD209 family.

Correspondence: ² Address correspondence and reprint requests to Prof. Jian-zhong Shao, Zhejiang University, YuHangTang Road, Hangzhou 310058, Zhejiang, People's Republic of China. E-mail address: shaojz{at}zju.edu.cn

¹ This work was supported by grants from the National Basic Research Program of China (973) (2006CB101805), Hi-Tech Research and Development Program of China (863) (2008AA09Z409), the National Natural Science Foundation of China (30871936 and 30571423), Zhejiang Natural Science Foundation (Z305039), and the Science and Technology Foundation of Zhejiang Province (2006C12038, 2006C 23045, 2006C 12005, and 2007C 12011).