Kinesin family member KIF18A is a critical cellular factor that regulates the differentiation and activation of dendritic cells

Abstract

Background KIF18A is a kinesin family member that is involved in various cellular processes including cell division, cell transformation, and carcinogenesis. However, its possible role in the regulation of host immunity has not been examined. Objective The aim of this study is to investigate the functional role of KIF18A in the differentiation and activation of dendritic cells (DCs) that are the most efficient antigen-presenting cells. Methods A bioinformatic analysis of the KIF18A gene family was performed to understand its sequence variability and evolutionary history. To inhibit KIF18A activity, a highly specific small molecule inhibitor for KIF18A, BTB-1 was used. DCs were differentiated from mouse bone marrow (BM) cells from 6 to 7 week old C57BL/6 mice with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Expression of KIF18A was measured by Western blotting. The surface expression of differentiation and activation markers on DCs were analyzed by flow cytometry. Results The phylogenetic analysis revealed that the KIF18A gene family is remarkably conserved across vertebrates. Interestingly, the expression of KIF18A was increased as BM precursor cells differentiated into DCs. BTB-1 treatment strongly inhibited the differentiation of BM cells into DCs in a dose-dependent manner. Furthermore, treatment of immature DCs with BTB-1 significantly impaired the expression of activation markers on DCs including MHC class I, CD80, and CD86 upon TLR4 or TLR7 treatment. Conclusion Our results reveal that KIF18A is a critical DC differentiation and activation regulator. Therefore, KIF18A could be a potential therapeutic target for immune-mediated disorders.