Both the RGD sequence and the cytoplasmic tail of ADAM15 are required for homotypic aggregation of T lymphocytes and heterotypic interactions between T lymphocytes and intestinal epithelia.

We previously showed that the RGD integrin-binding sequence-containing ADAM15 is expressed in intestinal epithelial cells (IEC). The presence of a RGD-containing disintegrin protein in IEC suggested a potential role of ADAM15 in cell adhesion involving these cells. As already described in NIH3T3 cells, our previous finding of the inhibition of IEC wound-healing by ADAM15 overexpression could-be due to enhanced cell-cell interactions. Therefore, our recent finding of ADAM15 up-regulation during inflammatory bowel disease (IBD) led us to examine the roles of ADAM15 in cell adhesion relevant to IBD. T cell adhesion on IEC was assessed using Jurkat cells and Caco2-BBE monolayers. Our results show that an anti-ADAM15 ectodomain antibody inhibited the binding of Jurkat cells on Caco2-BBE monolayers. Overexpression of ADAM15 in Caco2-BBE cells enhanced Jurkat cells binding and overexpression of ADAM15 in Jurkat cells enhanced homotypic adhesion. Both the mutation of the RGD domain and the deletion of the cytoplasmic tail decreased these cell-cell interactions. Here we demonstrate that 1) ADAM15 is involved in T cell adhesion to IEC as well as T cell aggregation; 2) both the RGD motif and the cytoplasmic tail of ADAM15 are involved for these cell-cell interactions. Altogether these findings point to ADAM15 as a possible. therapeutic target for prevention of inappropriate T cell activation involved in some pathologies. [ABSTRACT FROM AUTHOR]