Importance of PI3Ks in TLR9 signaling pathway

Although PI3Ks have important functions in cellular processes and the immune system, studies of the precise role of each PI3K in cellular biological and immune responses has been limited because of lack of specific inhibitors to individual PI3Ks. In the present study, we used kinase-dead mutants and synthetic phospholipids of PI3Ks to study the intracellular role of distinct PI3Ks in TLR9-mediated responses. Our results revealed that class III PI3K specifically regulates CpG oligodeoxynucleotide (ODN)/ TLR9-induced cytokine and NF-kB activation, whereas class I PI3K regulates both CpG ODN/TLR9- and LPS/TLR4-induced IL-12 production and NF-kB activation. Additional studies indicated that class III PI3K, but not class I, regulates cellular TLR9 ligand CpG ODN uptake. These results have been published on Journal of Immunology (2006, 176, pp. 5943-5949) and suggest that class I and class III PI3K play distinct roles in not only the uptake of CpG ODN, but also responses elicited by CpG ODN and LPS. Kuo, C.-C., Lin, W.-T., Liang, C.-M., Liang, S.-M.* (2006). Class I and III phosphatidylinositol 3’-kinase play distinct roles in Toll-like receptor signaling pathway. Journal of Immunology, 176, pp. 5943-5949.