CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions.

Molecular biology of the cell

PubMedID: 24006483

Azcutia V, Routledge M, Williams MR, Newton G, Frazier WA, Manica A, Croce KJ, Parkos CA, Schmider AB, Turman MV, Soberman RJ, Luscinskas FW. CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions. Mol Biol Cell. 2013;.
CD47 plays an important but incompletely understood role in the innate and adaptive immune responses. CD47, also called Integrin Associated Protein, has been demonstrated to associate "in cis" with ß1 and ß3 integrins. Here we tested the hypothesis that CD47 regulates adhesive functions of T-cell a4ß1 (VLA-4) and aLß2 (LFA-1) in in vivo and in vitro models of inflammation. Intravital microscopy studies revealed that CD47-/- Th1 cells exhibit reduced interactions with WT inflamed cremaster muscle microvessels. Similarly, murine CD47-/- Th1 cells, as compared with WT, showed defects in adhesion and transmigration across TNF-a-activated murine endothelium and in adhesion to immobilized ICAM-1 and VCAM-1 under flow conditions. Human Jurkat T-cells lacking CD47 also showed reduced adhesion to TNF-activated endothelium and immobilized ICAM-1 and VCAM-1. In cis interactions between Jurkat T-cell ß2 integrins and CD47 were detected by fluorescence lifetime imaging microscopy. Unexpectedly, Jurkat CD47- cells exhibited a striking defect in ß1 and ß2 integrin activation in response to Mn(2+) or Mg(2+)/EGTA treatments. Our results demonstrate that CD47 associates with ß2 integrins, and that CD47 is necessary to induce high-affinity conformations of LFA-1 and VLA-4 that recognize their endothelial cell ligands and support leukocyte adhesion and transendothelial migration.