Publications & Reports

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
Walter and Eliza Hall Institute of Medical Research Melbourne, Victoria 3050, Australia. caminschi@wehi.edu.au

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.

Publication

  • Journal: International Immunology
  • Published: 01/05/2006
  • Volume: 18
  • Issue: 5
  • Pagination: 741-753