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

• DOI: 10.1189/jlb.0608344
• Publication Date: 2009-04-16T01:54:15Z
• Authors: Annegret Reinhold; Sibylle Reimann; Dirk Reinhold; Burkhart Schraven; Mauro Togni
• Keywords: Mice, Knockout; Integrins; 0303 health sciences; Encephalomyelitis, Autoimmune, Experimental; Immunological Synapses; T-Lymphocytes; Immunity; Intracellular Signaling Peptides and Proteins; Antigen-Presenting Cells; Dendritic Cells; 3. Good health; Mice; 03 medical and health sciences; Cell Movement; Animals

Abstract The genetic deletion of SKAP-HOM, an ubiquitously expressed cytosolic adapter protein, affected DC:T cell interactions reducing immune response. adaptor molecule 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 absence antigen receptor-triggered integrin-mediated adhesion is impaired severely B cells but not cells. In addition, loss SKAP-HOM results a less severe clinical course EAE. DCs most potent APCs express SKAP-HOM. However, role remains unknown. Here, we assessed whether reduced severity EAE observed SKAP-HOM-deficient mice at least partially result cooperation between We demonstrate migration LC vivo spontaneous motility BMDCs vitro increased contrast, triggering integrin drastic decrease DC enhanced actin polymerization DCs. Furthermore, antigen-dependent conjugate formed wild-type SKAP-HOM−/− delayed comparison Strikingly, fewer antigen-specific induced by immunization as compared vivo. Thus, these findings suggest expression required for induction optimal