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

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 FcεRI, 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 FcεRI 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 FcεRI ^pos and FcεRI ^neg monocyte subpopulations was evaluated. Flow cytometry, confocal microscopy, immunoprecipitation, and immunoblotting experiments were performed to observe the relationship between tetraspanins CD9 and CD81 and FcεRI. Furthermore, plate stimulation experiments were performed, and cytokines in the supernatants were detected. Results: We found that human FcεRI ^pos APCs expressed high amounts of tetraspanins and that the tetraspanins CD9 and CD81 were associated with FcεRI. Concomitant activation of FcεRI and CD9 on human monocytes increased FcεRI-mediated cytokine release. Conclusion: Taken together, we show for the first time that CD9 and CD81 act as molecular partners of trimeric FcεRI on human APC, which might be of importance in allergic diseases such as AD.