Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN

Caminschi, I; Corbett, AJ; Zahra, C; Lahoud, M; Lucas, KM; Sofi, M; Vremec, D; Gramberg, T; Pohlmann, S; Curtis, J; Handman, E; van Dommelen, SLH; Fleming, P; Degli-Esposti, MA; Shortman, K; Wright, MD

Author(s): Caminschi, I; Corbett, AJ; Zahra, C; Lahoud, M; Lucas, KM; Sofi, M; Vremec, D; Gramberg, T; Pohlmann, S; Curtis, J; Handman, E; van Dommelen, SLH; Fleming, P; Degli-Esposti, MA; Shortman, K; Wright, MD;
Details: Publication Year 2006-05,Volume 18,Issue #5,Page 741-753
Journal Title: INTERNATIONAL IMMUNOLOGY
Publication Type: Journal Article
Abstract: CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (DC) populations. Immunostaining with a CIRE/mDC-SIGN-specific mAb revealed that CIRE/mDC-SIGN is indeed on the surface of some CD4(+), CD4(-)8(-) DCs and plasmacytoid pre-DCs, but not on CD8(+) DCs. It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC-SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC-SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression, indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T cell-DC interactions and the protein did not bind to pathogens known to interact with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the stalk region of hDC-SIGN. We conclude that there are significant differences in the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN and that these two molecules may not be functional orthologues.
Publisher: OXFORD UNIV PRESS
Keywords: C-TYPE LECTIN; DENDRITIC CELL SUBSETS; HUMAN-IMMUNODEFICIENCY-VIRUS; MARGINAL ZONE MACROPHAGES; PRIMARY IMMUNE-RESPONSES; CD4 T-CELLS; IN-VIVO; CUTTING EDGE; EBOLA-VIRUS; MOLECULAR-CLONING
Publisher's Version: https://doi.org/10.1093/intimm/dxl011
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Creation Date: 2006-05-01 12:00:00