Intestinal epithelial cells (IEC) play an immunoregulatory role in the intestine. This role involves cell-cell interactions with intraepithelial lymphocytes that may also play a role in some enteropathies. The discovery of the RGD motif-containing Protein ADAM-15 (a disintegrin and metalloprotease-15) raises the question of its involvement in these cell-cell interactions. Cell adhesion assays were performed using the Jurkat E6.1 T cell line as a model of T lymphocytes and Caco2-BBE monolayers as a model of intestinal epithelia. Our results show that an anti-ADAM-15 ectodomain antibody inhibited the attachment of Jurkat cells on Caco2-BBE monolayers. Overexpression of ADAM-15 in Caco2-BBE cells enhanced Jurkat cell binding, and overexpression of ADAM-15 in Jurkat cells enhanced their aggregation. Mutagenesis experiments showed that both the mutation of ADAM-15 RGD domain or the deletion of its cytoplasmic tail decreased these cell-cell interactions. Moreover, wound-healing experiments showed that epithelial ADAM-15-mediated Jurkat cell adhesion to Caco2-BBE cells enhances the mechanisms of wound repair. We also found that ADAM-15-mediated aggregation of Jurkat cells increases the expression of tumor necrosis factor-α mRNA. These results demonstrate the following: 1) ADAM-15 is involved in heterotypic adhesion of intraepithelial lymphocytes to IEC as well as in homotypic aggregation of T cells; 2) both the RGD motif and the cytoplasmic tail of ADAM-15 are involved for these cell-cell interactions; and 3) ADAM-15-mediated cell-cell interactions are involved in mechanisms of epithelial restitution and production of pro-inflammatory mediators. Altogether these findings point to ADAM-15 as a possible therapeutic target for prevention of inappropriate T cell activation involved in some pathologies. Intestinal epithelial cells (IEC) play an immunoregulatory role in the intestine. This role involves cell-cell interactions with intraepithelial lymphocytes that may also play a role in some enteropathies. The discovery of the RGD motif-containing Protein ADAM-15 (a disintegrin and metalloprotease-15) raises the question of its involvement in these cell-cell interactions. Cell adhesion assays were performed using the Jurkat E6.1 T cell line as a model of T lymphocytes and Caco2-BBE monolayers as a model of intestinal epithelia. Our results show that an anti-ADAM-15 ectodomain antibody inhibited the attachment of Jurkat cells on Caco2-BBE monolayers. Overexpression of ADAM-15 in Caco2-BBE cells enhanced Jurkat cell binding, and overexpression of ADAM-15 in Jurkat cells enhanced their aggregation. Mutagenesis experiments showed that both the mutation of ADAM-15 RGD domain or the deletion of its cytoplasmic tail decreased these cell-cell interactions. Moreover, wound-healing experiments showed that epithelial ADAM-15-mediated Jurkat cell adhesion to Caco2-BBE cells enhances the mechanisms of wound repair. We also found that ADAM-15-mediated aggregation of Jurkat cells increases the expression of tumor necrosis factor-α mRNA. These results demonstrate the following: 1) ADAM-15 is involved in heterotypic adhesion of intraepithelial lymphocytes to IEC as well as in homotypic aggregation of T cells; 2) both the RGD motif and the cytoplasmic tail of ADAM-15 are involved for these cell-cell interactions; and 3) ADAM-15-mediated cell-cell interactions are involved in mechanisms of epithelial restitution and production of pro-inflammatory mediators. Altogether these findings point to ADAM-15 as a possible therapeutic target for prevention of inappropriate T cell activation involved in some pathologies. Intestinal epithelial cells (IEC) 3The abbreviations used are: IEC, intestinal epithelial cells; IBD, inflammatory bowel disease; TNF, tumor necrosis factor; PBS, phosphate-buffered saline; BCECF-AM, 2′,7′-bis-(2-carboxyethyl)-5 (and-6) carboxyfluorescein, acetoxymethyl ester; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Tricine, N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine; Vect, vector. play an important role for the immune response within the intestinal tract. This immunoregulatory role of IEC is mediated through interactions with intestinal intraepithelial lymphocytes. The interactions between IEC and intraepithelial lymphocytes are thought to mediate T cell recruitment to intestinal epithelia (1Agace W.W. Higgins J.M. Sadasivan B. Brenner M.B. Parker C.M. Curr. Opin. Cell Biol. 2000; 12: 563-568Crossref PubMed Scopus (132) Google Scholar). In particular, cell-to-cell interactions are believed to stabilize the retention of lymphocytes within intestinal epithelia (2Cepek K.L. Shaw S.K. Parker C.M. Russell G.J. Morrow J.S. Rimm D.L. Brenner M.B. Nature. 1994; 372: 190-193Crossref PubMed Scopus (974) Google Scholar), thus leading to the formation of an immune barrier against intestinal pathogens. However, aberrant cell adhesion has been implicated in the pathogenesis of a number of inflammatory disorders, including inflammatory bowel disease (IBD). Among immune cells recruited during intestinal inflammation, T lymphocytes may play a role in the pathogenesis of various intestinal diseases including Crohn disease and ulcerative colitis. Indeed some intestinal diseases show increased intraepithelial lymphocytes (i.e. celiac disease, lymphocytic colitis, tropical sprue, and giardiasis) and/or phenotypic alteration of intraepithelial lymphocytes (celiac disease, Crohn disease, and ulcerative colitis) (3Ferguson A. McClure J.P. Townley R.R. Acta Paediatr. Scand. 1976; 65: 541-546Crossref PubMed Scopus (67) Google Scholar, 4Fukushima K. Masuda T. Ohtani H. Sasaki I. Funayama Y. Matsuno S. Nagura H. Gastroenterology. 1991; 101: 670-678Abstract Full Text PDF PubMed Scopus (62) Google Scholar, 5Halstensen T.S. Scott H. Brandtzaeg P. Scand. J. Immunol. 1989; 30: 665-672Crossref PubMed Scopus (301) Google Scholar, 6Halstensen T.S. Scott H. Brandtzaeg P. Eur. J. Immunol. 1990; 20: 1825-1830Crossref PubMed Scopus (56) Google Scholar, 7Lazenby A.J. Yardley J.H. Giardiello F.M. Jessurun J. Bayless T.M. Hum. Pathol. 1989; 20: 18-28Crossref PubMed Scopus (428) Google Scholar, 8Maki M. Holm K. Collin P. Savilahti E. Gut. 1991; 32: 1412-1414Crossref PubMed Scopus (173) Google Scholar, 9Ross I.N. Mathan V.I. Q. J. Med. 1981; 50: 435-449PubMed Google Scholar, 10Spencer J. MacDonald T.T. Diss T.C. Walker-Smith J.A. Ciclitira P.J. Isaacson P.G. Gut. 1989; 30: 339-346Crossref PubMed Scopus (153) Google Scholar, 11Vinayak V.K. Khanna R. Kum K. Microb. Pathog. 1991; 10: 343-350Crossref PubMed Scopus (13) Google Scholar). Most descriptions of early Crohn disease lesions include mucosal lymphoid aggregates (12Rickert R.R. Carter H.W. J. Clin. Gastroenterol. 1980; 2: 11-19Crossref PubMed Scopus (86) Google Scholar, 13Fujimura Y. Kamoi R. Iida M. Gut. 1996; 38: 724-732Crossref PubMed Scopus (123) Google Scholar, 14Borley N.R. Mortensen N.J. Jewell D.P. Warren B.F. J. Pathol. 2000; 190: 196-202Crossref PubMed Scopus (119) Google Scholar, 15Naganuma M. Watanabe M. Kanai T. Iwao Y. Mukai M. Ishii H. Hibi T. Am. J. Gastroenterol. 2002; 97: 1741-1747Crossref PubMed Google Scholar, 16Sanders D.S. J. Clin. Pathol. 2005; 58: 568-572Crossref PubMed Scopus (76) Google Scholar) that are mainly composed of T cells and that may contribute to the pathogenesis of Crohn disease (15Naganuma M. Watanabe M. Kanai T. Iwao Y. Mukai M. Ishii H. Hibi T. Am. J. Gastroenterol. 2002; 97: 1741-1747Crossref PubMed Google Scholar). Thus, it is interesting to consider the cell-cell interactions involved in IBD and possible strategies for therapeutic modulation. Only a few molecular interactions been that are involved in the retention of lymphocytes in intestinal epithelia. has been that of T lymphocytes to epithelial cell mediated through and J. J.P. Eur. J. Immunol. 1991; PubMed Scopus Google Scholar, J. Biol. Full Text Full Text PDF PubMed Scopus (153) Google Scholar, H. PubMed Scopus Google Scholar). on IEC, T interactions A. J. Med. PubMed Scopus Google Scholar). and Protein adhesion assays showed that on T cells T adhesion (2Cepek K.L. Shaw S.K. Parker C.M. Russell G.J. Morrow J.S. Rimm D.L. Brenner M.B. Nature. 1994; 372: 190-193Crossref PubMed Scopus (974) Google Scholar, K.L. Parker C.M. Brenner M.B. J. Immunol. Google Scholar, K. P.J. Eur. J. Immunol. PubMed Scopus Google Scholar, P.J. Eur. J. Immunol. PubMed Scopus Google Scholar, J.M. Shaw S.K. Russell G.J. Parker C.M. Brenner M.B. J. Cell Biol. PubMed Scopus Google Scholar, J.M. M. K. A. J. Y. Brenner M.B. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, Higgins J.M. K. J.H. Brenner M.B. J. Med. 2000; PubMed Scopus Google Scholar). has also been to involved in the heterotypic adhesion of T cells to epithelia H. A. J.S. 2002; PubMed Scopus Google Scholar) as well as in T cell homotypic adhesion K. J. T. M. J. Full Text Full Text PDF PubMed Scopus Google Scholar). The (a disintegrin and also are a of that with S. A. 1994; PubMed Scopus Google Scholar, P. J.M. Biol. PubMed Scopus Google Scholar). Among the ADAM-15 is the that has an RGD motif J. J. Biol. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar), a role of ADAM-15 in and in cell-cell interactions. has been that the disintegrin domain of ADAM-15 in an T. K. Y. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A. A.J. J. Cell PubMed Google Scholar) and with of the RGD motif K. A. Y. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). In overexpression of ADAM-15 in the cell line has been found to cell-cell interactions B. S. R. Cell PubMed Scopus Google Scholar). ADAM-15 has also been to in lymphocytes as well as cell including Jurkat cells J. J. Biol. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, E. PubMed Scopus Google Scholar, A. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). We that IEC ADAM-15 on the cell Y. A. Am. J. 2005; PubMed Scopus Google Scholar), and also found that during IBD ADAM-15 is and IEC are in with A. PubMed Scopus Google Scholar). These findings a role for ADAM-15 in that during Our to ADAM-15 in cell-cell interactions between IEC and T lymphocytes. Cell and Cell Caco2-BBE cell line Cell Biol. PubMed Scopus Google Scholar, M. S. A. Am. J. Pathol. Full Text Full Text PDF PubMed Scopus Google Scholar, A. S. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, S. A. J. PubMed Scopus Google Scholar) that cells M. S. The T cell line Jurkat E6.1 the Caco2-BBE cells were in with and Caco2-BBE cells were in the Jurkat E6.1 cells were in with and Jurkat cells were in the were in and adhesion assays with Jurkat Caco2-BBE cells were on and experiments were performed aggregation Jurkat cells were in to a of cells Cell cells were as with and cells were and in were to for cells or were for in with The were for and the were for Protein were using the Protein were in for on a or an and to were or for with in and with a antibody against the cytoplasmic tail of ADAM-15 or with a antibody against the were with an antibody were and were on using an enhanced to the cells were in for cell and with a in for and for The in through an Protein in the and in with the Caco2-BBE ADAM-15 and Caco2-BBE with a to the The of of with and with an of the used as a for The ADAM-15 using the and an for for the for for and for a of for for and for The on in The an of with the and its the expression the were using the and and The expression the of with the the of the expression of the of with a antibody of ADAM-15 ADAM-15 were The mutation of the RGD motif of ADAM-15 performed with the the the RGD motif an The deletion of the cytoplasmic tail also performed a in the cytoplasmic tail with the Caco2-BBE and Jurkat cells were with the as well as with the the ADAM-15 or its of Caco2-BBE Caco2-BBE cells were with or with using to the for in were in of Jurkat cells were with or with with to the a cell of in with using of for cells were in cells were with 2′,7′-bis-(2-carboxyethyl)-5 (and-6) carboxyfluorescein, acetoxymethyl in for these Jurkat as well as Caco2-BBE cells in were with their with or anti-ADAM-15 against the ectodomain or antibody with the for of Caco2-BBE Jurkat cells were cells in of to Caco2-BBE cells and for of Jurkat cells with Caco2-BBE the Jurkat cells were and cells in the were in and in a The using a with cells were as cells were with are as number of Jurkat cells on Caco2-BBE on with of Jurkat Cell Jurkat cells were in a of cells in well and in and were point and with a with a and a These were through a of using the Cell aggregates were and the of the for the of of cell aggregates cell were to for of cell aggregates cell were are as the of aggregates assays were performed with the Y. A. Am. J. 2005; PubMed Scopus Google Scholar). The model used for these The of an with the for cell well a and a the of with an to between the and a the and the The and of cells on the the in a that of the cells Caco2-BBE cells and Jurkat cells were in with a of in with and cell were for in Jurkat cells were cells were performed for using the for Caco2-BBE Y. A. Am. J. 2005; PubMed Scopus Google Scholar) and for the the wound-healing cells were to an of and a that to and of cells on the in a wound that is cells the that been to the cell aggregation assays were performed as of cells using using the and using the and the for of for and for with expression were used as a The used are as and and of for were the for using the as and were Scopus Google Scholar). the experiments and are as the of in used to of the in The of Jurkat to Caco2-BBE an against the that ADAM-15 is in and in the intestinal epithelial cell line Caco2-BBE Y. A. Am. J. 2005; PubMed Scopus Google Scholar). ADAM-15 has been to to and in an on cells A. A.J. J. Cell PubMed Google Scholar), the role of ADAM-15 in cell-cell interactions of lymphocytes. performed adhesion assays of Jurkat with the on Caco2-BBE as and lymphocytes as well as cell including ADAM-15 1) J. J. Biol. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, E. PubMed Scopus Google Scholar, A. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar), both Caco2-BBE and Jurkat cell were with or of anti-ADAM-15 antibody against ADAM-15 ectodomain or with a Jurkat cells were to Caco2-BBE and of Jurkat cells to Caco2-BBE monolayers the of that anti-ADAM-15 antibody inhibited Jurkat cell to Caco2-BBE cells cells In the antibody on Jurkat cell attachment cells These results that ADAM-15 is involved in antibody Jurkat cell attachment on Caco2-BBE assays were performed with Caco2-BBE cell line as an and Jurkat cells as cells in the or of anti-ADAM-15 antibody or antibody the number of Jurkat cells on Caco2-BBE monolayers and are as the of This is of Overexpression of ADAM-15 in Caco2-BBE the of Jurkat epithelial and/or T ADAM-15 is involved in cell-cell performed cell adhesion assays using Caco2-BBE ADAM-15 and Jurkat cells or Caco2-BBE cells and Jurkat cells Caco2-BBE cells were with the expression or the ADAM-15 number Y. A. Am. J. 2005; PubMed Scopus Google Scholar) with the performed on cell cells with antibody showed that ADAM-15 in Caco2-BBE cells assays of Jurkat cells were performed on and that overexpression of ADAM-15 in Caco2-BBE cells enhanced Jurkat cells with Caco2-BBE monolayers cells on monolayers cells on This that ADAM-15 on Caco2-BBE cells are involved in the with Jurkat Overexpression of ADAM-15 in Jurkat ADAM-15 on Jurkat cells is also involved in the with Caco2-BBE Jurkat cells were also with ADAM-15 number Y. A. Am. J. 2005; PubMed Scopus Google Scholar) or with the performed on cell with showed that ADAM-15 in Jurkat cells assays of or cells were performed on Caco2-BBE overexpression of ADAM-15 the cell of Jurkat cells decreased the of Jurkat cells with Caco2-BBE cells cells We the for decreased adhesion of cells to Caco2-BBE We that cells aggregates cells to the role of ADAM-15 in the formation of these performed homotypic cell adhesion and cells were as a the in and were the of cell and the of cell aggregates that cell point both and cells were as a both to aggregates of and However, the cells were the cells for cells for cells and for cells for cells These findings that ADAM-15 a role in T of ADAM-15 in Jurkat cells enhances homotypic the of cells with ADAM-15 to aggregates with Jurkat cells with the during cell aggregation assays were performed as and using and as well as Jurkat cells with ADAM-15 the RGD or the cytoplasmic tail were as a This is of well of cell through a of using the as and of cell aggregates cell were are as the of aggregates and for These also an for the decreased number of cells that to Caco2-BBE monolayers in with the number of during heterotypic cell experiments cells are to to of to Caco2-BBE ADAM-15 RGD and in between Caco2-BBE and Jurkat the molecular mechanisms ADAM-15-mediated cell-cell interactions between IEC and T Caco2-BBE cells with ADAM-15 ADAM-15 the RGD motif or the cytoplasmic tail were as and of Caco2-BBE cells with these ADAM-15 and that these ADAM-15 were We performed heterotypic cell using Caco2-BBE monolayers and Jurkat in both the mutation of the RGD and the deletion of the cytoplasmic tail ADAM-15-mediated of Jurkat cell adhesion to Caco2-BBE monolayers This that both the RGD and the cytoplasmic domain are for these ADAM-15-mediated cell-cell interactions. ADAM-15 RGD and in ADAM-15-mediated T Cell the molecular mechanisms of ADAM-15-mediated T cell aggregation. Jurkat cells were with the ADAM-15 and the were for ADAM-15 expression cell-cell assays were performed using these Jurkat cells as and We found that Jurkat cells ADAM-15 with a RGD to aggregates as for the Jurkat cells and The deletion of the cytoplasmic tail ADAM-15-mediated of Jurkat cell aggregation for cells for cells and for cells for cells and These results that both the RGD motif and the cytoplasmic tail are involved in T cell homotypic interactions and that the RGD is for the of cell-cell interactions. ADAM-15-mediated of between Caco2-BBE and Jurkat with intestinal inflammation, intestinal also epithelial We ADAM-15-mediated cell-cell interactions between Caco2-BBE and Jurkat cells the of wound repair. Caco2-BBE cells were and with Jurkat cells or in with of as and cells were performed for and cells were to an leading to a in cells a that of the the formation of the that for cells with wound-healing is within the However, in with findings Y. A. Am. J. 2005; PubMed Scopus Google Scholar), overexpression of ADAM-15 in Caco2-BBE cells inhibited the mechanisms of wound with found that mutation of ADAM-15 RGD motif or deletion of the cytoplasmic cells that were with and were to the in the as cells These findings that both the RGD and the cytoplasmic tail are involved in ADAM-15-mediated of wound Y. A. Am. J. 2005; PubMed Scopus Google Scholar). also that and cells were with Jurkat the the of Jurkat cells and However, for the of Jurkat cells increased the of cell in with cells in the of and also in with and cells with Jurkat cells and these findings with the of Jurkat cell adhesion on the Caco2-BBE cells This that epithelial ADAM-15-mediated cell adhesion of T lymphocytes to IEC increases wound-healing ADAM-15-mediated of T with an of lymphoid aggregates are during intestinal (12Rickert R.R. Carter H.W. J. Clin. Gastroenterol. 1980; 2: 11-19Crossref PubMed Scopus (86) Google Scholar, 13Fujimura Y. Kamoi R. Iida M. Gut. 1996; 38: 724-732Crossref PubMed Scopus (123) Google Scholar, 14Borley N.R. Mortensen N.J. Jewell D.P. Warren B.F. J. Pathol. 2000; 190: 196-202Crossref PubMed Scopus (119) Google Scholar, 15Naganuma M. Watanabe M. Kanai T. Iwao Y. Mukai M. Ishii H. Hibi T. Am. J. Gastroenterol. 2002; 97: 1741-1747Crossref PubMed Google Scholar, 16Sanders D.S. J. Clin. Pathol. 2005; 58: 568-572Crossref PubMed Scopus (76) Google Scholar), the of ADAM-15-mediated aggregation of T lymphocytes on is a that a role in D.S. J. Clin. Pathol. 2005; 58: 568-572Crossref PubMed Scopus (76) Google Scholar). T cell homotypic adhesion assays were performed as using the of Jurkat and of cells were and for expression that overexpression of ADAM-15 the of in cells to in with cells with the However, for cells with ADAM-15 the RGD motif or the cytoplasmic tail the expression of decreased the for both the RGD motif and the cytoplasmic tail of The of to the role of ADAM-15 in heterotypic cell-cell interactions between IEC and T lymphocytes. interactions play an important role in of These interactions are involved in cell and activation The of recruitment the the also the of these the and their the epithelial a in adhesion on cells as well as on lymphocytes. We that ADAM-15 is in IEC Y. A. Am. J. 2005; PubMed Scopus Google Scholar). lymphocytes as well as cell including been to ADAM-15 J. J. Biol. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, E. PubMed Scopus Google Scholar, A. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google and ADAM-15 an RGD motif in its disintegrin domain J. J. Biol. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar) that has been to mediate the of ADAM-15 to and on cells A. A.J. J. Cell PubMed Google Scholar). Our results show for the that ADAM-15 is involved in heterotypic cell-cell interactions between IEC and T lymphocytes. Jurkat cell attachment to Caco2-BBE monolayers inhibited an anti-ADAM-15 antibody against the ectodomain of ADAM-15 overexpression in Caco2-BBE cells enhanced Jurkat cell adhesion to Caco2-BBE monolayers. These results that epithelial ADAM-15 to that on the cell of T lymphocytes. Our that overexpression of ADAM-15 with a mutation in the RGD motif in Caco2-BBE monolayers Jurkat cell adhesion that ADAM-15-mediated of T cells on IEC is on the RGD This to and as the epithelial ADAM-15 on T in experiments that the disintegrin domain of ADAM-15 with and on cells A. A.J. J. Cell PubMed Google Scholar) and that ADAM-15 with these in a T. K. Y. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, A. A.J. J. Cell PubMed Google Scholar). However, the findings that and are or in the intestinal J. Cell PubMed Google Scholar, R. R. J. Cell Biol. PubMed Scopus Google Scholar, Y. J. PubMed Scopus Google Scholar, Y. 2000; PubMed Scopus Google Scholar) are in of an involvement of T ADAM-15 in cell-cell interactions between IEC and T lymphocytes. cell adhesion assays using Jurkat cells with ADAM-15 to the role of ADAM-15 on T cells in heterotypic cell-cell interactions with However, these experiments to of ADAM-15 involvement in cell-cell interactions and ADAM-15 as involved in aggregation of T This an for the results in the heterotypic cell adhesion assays using Caco2-BBE cells and Jurkat cells and is in with a that overexpression of ADAM-15 in the cell line enhances homotypic cell-cell interactions B. S. R. Cell PubMed Scopus Google Scholar). This the that lymphocytes both ADAM-15 and of its and J. J. Biol. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T. K. Y. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, K. A. Y. J. Biol. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, E. PubMed Scopus Google Scholar, A. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). Moreover, that Jurkat cell aggregation on the RGD motif that these are ADAM-15 involved in these cell-cell interactions. T cell ADAM-15 may a role in or the interactions that the formation of an or that important for the of involved in T cell This is the that the cytoplasmic tail of ADAM-15 in immune cells A. J. Biol. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). In it is that are also to in T cells M. K. A. J. Cell PubMed Scopus Google Scholar). Our results show that ADAM-15 cytoplasmic tail is also for the of both heterotypic and homotypic cell-cell interactions. We found that Jurkat cell attachment to Caco2-BBE monolayers decreased Caco2-BBE cells ADAM-15 with a cytoplasmic tail in with the attachment to Caco2-BBE monolayers ADAM-15 the deletion of the ADAM-15 cytoplasmic tail of Jurkat cell aggregation. These results that the ADAM-15 ectodomain also the cytoplasmic domain play a role in cell-cell through that or cell-cell interactions. The in Jurkat cell aggregation between cells ADAM-15 with a RGD or with a cytoplasmic tail that ADAM-15 to through the RGD is the for these cell-cell interactions. Our that Jurkat cells ADAM-15 with a cytoplasmic tail aggregates Jurkat cells with the that in the of cytoplasmic the that the formation of T cell aggregates are or The of these findings in the that lymphoid aggregates are during intestinal (12Rickert R.R. Carter H.W. J. Clin. Gastroenterol. 1980; 2: 11-19Crossref PubMed Scopus (86) Google Scholar, 13Fujimura Y. Kamoi R. Iida M. Gut. 1996; 38: 724-732Crossref PubMed Scopus (123) Google Scholar, 14Borley N.R. Mortensen N.J. Jewell D.P. Warren B.F. J. Pathol. 2000; 190: 196-202Crossref PubMed Scopus (119) Google Scholar, 15Naganuma M. Watanabe M. Kanai T. Iwao Y. Mukai M. Ishii H. Hibi T. Am. J. Gastroenterol. 2002; 97: 1741-1747Crossref PubMed Google Scholar, 16Sanders D.S. J. Clin. Pathol. 2005; 58: 568-572Crossref PubMed Scopus (76) Google Scholar) and in that ADAM-15-mediated T cell aggregation with increased expression of is an important involved in intestinal D.S. J. Clin. Pathol. 2005; 58: 568-572Crossref PubMed Scopus (76) Google Scholar). mutation of the RGD domain or deletion of the cytoplasmic cell aggregation or the expression of overexpression of the of expression these cells aggregates cells with the This to the that in the of ADAM-15 in cells is to to a of However, the of found in cells with ADAM-15 that ADAM-15 is involved in the of Moreover, found that mutation of the RGD motif and deletion of the cytoplasmic tail to an of mutation of the RGD domain the formation of cell and deletion of the cytoplasmic tail cell aggregation. This that the of expression on cell aggregation also on ADAM-15-mediated cell are to the mechanisms of ADAM-15-mediated of expression in T Our that ADAM-15 is to mediate heterotypic cell-cell interactions between T lymphocytes and IEC, as well as T homotypic cell-cell interactions. been to mediate and heterotypic cell-cell interactions. has been to involved in T cell aggregation K. J. T. M. J. Full Text Full Text PDF PubMed Scopus Google Scholar) as well as in heterotypic adhesion of T cells to epithelia H. A. J.S. 2002; PubMed Scopus Google Scholar). is also to mediate homotypic adhesion of R. J. Med. PubMed Scopus Google Scholar) and homotypic adhesion of J. Immunol. Google Scholar), as well as heterotypic cell-cell interactions between T lymphocytes and cells P. T. M. J. Immunol. Google Scholar). interactions of are important in the of immune as or T E. S. A. PubMed Scopus Google Scholar, H. H. M. PubMed Scopus Google Scholar). is interesting to that ADAM-15-mediated cell adhesion involved in Our A. PubMed Scopus Google Scholar) of ADAM-15 during IBD and the of ADAM-15 and its an involvement of ADAM-15 in and that a of In demonstrate that ADAM-15 a role in T cell adhesion to In wound-healing experiments on Caco2-BBE cells with Jurkat cells showed that Jurkat cells wound mechanisms and that involves The between the of Jurkat cell attachment on the Caco2-BBE cell and the of Jurkat cells on wound that epithelial ADAM-15-mediated cell adhesion of T lymphocytes to IEC mechanisms of repair. These findings are of intestinal is of the intestinal is epithelial The mechanisms of T of wound through ADAM-15 to However, that to the that T lymphocytes with IEC for interactions with to decreased homotypic cell-cell interactions between IEC and increased of is also possible that T cells adhesion to IEC through ADAM-15 and that IEC wound been and include Cell 1996; PubMed Scopus Google Scholar) as well as is increased in Crohn disease S. T. K. J.M. H. A. A. S. K. J. T. B. J. Am. J. PubMed Scopus Google Scholar). are to the molecular mechanisms ADAM-15-mediated homotypic T cell adhesion and heterotypic cell-cell interactions of T cells with The mechanisms of expression and epithelial restitution to these to as Altogether these results ADAM-15 as a important involved in both homotypic and heterotypic cell-cell interactions and point to ADAM-15 as a of T during intestinal These also ADAM-15 as a possible target in the prevention of inappropriate T cell activation in some pathologies. We of of cells and for the on the
No takes yet. Share an insight, caveat, or question.
Charrier et al. (2007) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: