Tetraspanins CD9 and CD81 are molecular partners of trimeric FcεRI on human antigen-presenting cells

P>Background: Most functions of tetraspanins are not related to cell-surface receptor ligand binding, but are mediated by direct interactions with their partner proteins. Functions of trimeric Fc epsilon RI, expressed by antigen-presenting cells (APCs), range from amplification of allergic inflammatory reactions to their active suppression. Cell-type-specific protein-protein interactions might play a role in the regulation of these bidirectional tasks. Therefore, we intended to study the interactions of trimeric Fc epsilon RI with tetraspanins. Methods: The expression levels of tetraspanins CD9, CD37, CD53, CD63, CD81, CD82, and CD151 on skin dendritic cells of atopic dermatitis (AD) patients or healthy individuals were detected by flow cytometry. Tetraspanin expression on Fc epsilon RIpos and Fc epsilon RIneg monocyte subpopulations was evaluated. Flow cytometry, confocal microscopy, immunoprecipitation, and immunoblotting experiments were performed to observe the relationship between tetraspanins CD9 and CD81 and Fc epsilon RI. Furthermore, plate stimulation experiments were performed, and cytokines in the supernatants were detected. Results: We found that human Fc epsilon RIpos APCs expressed high amounts of tetraspanins and that the tetraspanins CD9 and CD81 were associated with Fc epsilon RI. Concomitant activation of Fc epsilon RI and CD9 on human monocytes increased Fc epsilon RI-mediated cytokine release. Conclusion: Taken together, we show for the first time that CD9 and CD81 act as molecular partners of trimeric Fc epsilon RI on human APC, which might be of importance in allergic diseases such as AD.