Migration of immature mouse DC across resting endothelium is mediated by ICAM‐2 but independent of β₂‐integrins and murine DC‐SIGN homologues

Abstract

Immature dendritic cells (DC) reside in tissues where they initiate immune responses by taking up foreign antigens. Since DC have a limited tissue half-life, the DC pool in tissues has to be replenished constantly. This implies that precursor/immature DC must be able to cross non-activated endothelium using as yet unknown mechanisms. Here we show that immature, but not mature bone marrow-derived murine DC migrate across resting endothelial monolayers in vitro. We find that endothelial intercellular adhesion molecule-2 (ICAM-2) is a major player in transendothelial migration (TEM) of immature DC, accounting for at least 41% of TEM. Surprisingly, the ICAM-2-mediated TEM was independent of b 2 -integrins, the known ICAM-2 ligands, since neither blocking of b 2 -integrins with antibodies nor the use of CD18-deficient DC affected the ICAM-2-specific TEM. In humans, the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) was shown to interact with ICAM-2, suggesting a similar role in mice. However, we find that none of the murine DC-SIGN homologues mDC-SIGN, murine DC-SIGN-related molecule-1 (mSIGN-R1) and mSIGN-R3 is expressed on the surface of bone marrow-derived mouse DC. Taken together, this study shows that ICAM-2 strongly supports transmigration of immature DC across resting endothelium by interacting with ligands that are distinct from b 2 -integrins and DC-SIGN homologues.

T Cell–Extrinsic CD18 Attenuates Antigen-Dependent CD4+ T Cell Activation In Vivo

“…These combined outcomes indicate that migration of APC to CD18 −/− PLN is intact. This is consistent with most, but not all (19,33), studies showing that transendothelial migration of mouse (34) and human (35) DC can be independent of β2 integrins. Similarly, migration of CD18 −/− DC to skin at sites of acute contact dermatitis in mice is normal (12).…”

Porcine DC-SIGN: Molecular cloning, gene structure, tissue distribution and binding characteristics

“…This is partly due to the fact that mouse does not have the ICAM-3 homologue in its genome [40]. Moreover, mouse SIGNRs 1, 3 and 5 do not interact with mouse ICAM-2 and do not support ICAM-2 mediated transmigration of immature DCs across resting endothelium [41]. SIGNR5 plays no role in T cell-DCs interactions and did not bind to pathogens known to interact with hDC-SIGN [42].…”

Mechanisms and Consequences of Dendritic Cell Migration

“…Some information may be gleaned from in vitro experiments. For example, a recent study found a role for the IgSF molecule ICAM-2 in the transmigration of immature DCs across endothelial monolayers (Wethmar et al, 2006). …”