Expression of SKAP-HOM in DCs is required for an optimal immune response in vivo. Export

@article{citeulike:4350440, abstract = {The cytosolic adaptor molecule SKAP-HOM, similar to the T cell-specific homologue SKAP55, interacts directly with ADAP, and both molecules are involved in inside-out signaling. Previous studies have shown that in the absence of SKAP-HOM, antigen receptor-triggered integrin-mediated adhesion is impaired severely in B cells but not in T cells. In addition, loss of SKAP-HOM results in a less-severe clinical course of EAE. DCs are the most potent APCs and express SKAP-HOM. However, the role of SKAP-HOM in DCs remains unknown. Here, we assessed whether the reduced severity of EAE observed in SKAP-HOM-deficient mice is at least partially a result of an impaired cooperation between APCs and T cells. We demonstrate that migration of LC in vivo and the spontaneous motility of BMDCs in vitro are increased in the absence of SKAP-HOM. In contrast, triggering of the integrin results in a drastic decrease of DC motility and in enhanced actin polymerization in SKAP-HOM-deficient DCs. Furthermore, the antigen-dependent conjugate formed between wild-type T cells and SKAP-HOM(-/-) DCs is delayed in comparison with wild-type DCs. Strikingly, fewer antigen-specific T cells are induced by immunization with SKAP-HOM(-/-) BMDCs as compared with wild-type BMDCs in vivo. Thus, these findings suggest that SKAP-HOM expression in DCs is required for the induction of an optimal immune response.}, author = {Reinhold, Annegret and Reimann, Sibylle and Reinhold, Dirk and Schraven, Burkhart and Togni, Mauro}, citeulike-article-id = {4350440}, citeulike-linkout-0 = {http://dx.doi.org/10.1189/jlb.0608344}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19369640}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19369640}, day = {15}, doi = {10.1189/jlb.0608344}, issn = {1938-3673}, journal = {Journal of leukocyte biology}, keywords = {dc, skap55}, month = {April}, posted-at = {2009-04-17 22:11:28}, priority = {2}, title = {Expression of SKAP-HOM in DCs is required for an optimal immune response in vivo.}, url = {http://dx.doi.org/10.1189/jlb.0608344}, year = {2009} }

TY - JOUR ID - citeulike:4350440 L3 - citeulike-article-id:4350440 N2 - The cytosolic adaptor molecule SKAP-HOM, similar to the T cell-specific homologue SKAP55, interacts directly with ADAP, and both molecules are involved in inside-out signaling. Previous studies have shown that in the absence of SKAP-HOM, antigen receptor-triggered integrin-mediated adhesion is impaired severely in B cells but not in T cells. In addition, loss of SKAP-HOM results in a less-severe clinical course of EAE. DCs are the most potent APCs and express SKAP-HOM. However, the role of SKAP-HOM in DCs remains unknown. Here, we assessed whether the reduced severity of EAE observed in SKAP-HOM-deficient mice is at least partially a result of an impaired cooperation between APCs and T cells. We demonstrate that migration of LC in vivo and the spontaneous motility of BMDCs in vitro are increased in the absence of SKAP-HOM. In contrast, triggering of the integrin results in a drastic decrease of DC motility and in enhanced actin polymerization in SKAP-HOM-deficient DCs. Furthermore, the antigen-dependent conjugate formed between wild-type T cells and SKAP-HOM(-/-) DCs is delayed in comparison with wild-type DCs. Strikingly, fewer antigen-specific T cells are induced by immunization with SKAP-HOM(-/-) BMDCs as compared with wild-type BMDCs in vivo. Thus, these findings suggest that SKAP-HOM expression in DCs is required for the induction of an optimal immune response. JF - Journal of leukocyte biology SN - 1938-3673 TI - Expression of SKAP-HOM in DCs is required for an optimal immune response in vivo. KW - dc KW - skap55 AU - Reinhold, Annegret AU - Reimann, Sibylle AU - Reinhold, Dirk AU - Schraven, Burkhart AU - Togni, Mauro PY - 2009/04/15/ UR - http://dx.doi.org/10.1189/jlb.0608344 ER -