| First Author | Lima BHF | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 19085 |
| PubMed ID | 31836766 | Mgi Jnum | J:297716 |
| Mgi Id | MGI:6479189 | Doi | 10.1038/s41598-019-55504-0 |
| Citation | Lima BHF, et al. (2019) Converging TLR9 and PI3Kgamma signaling induces sterile inflammation and organ damage. Sci Rep 9(1):19085 |
| abstractText | Toll-like receptor 9 (TLR9) and Phosphatidylinositol-3-kinase gamma (PI3Kgamma) are very important effectors of the immune response, however, the importance of such crosstalk for disease development is still a matter of discussion. Here we show that PI3Kgamma is required for immune responses in which TLR9 is a relevant trigger. We demonstrate the requirement of PI3Kgamma for TLR9-induced inflammation in a model of CpG-induced pleurisy. Such requirement was further observed in inflammatory models where DNA sensing via TLR9 contributes to disease, such as silicosis and drug-induced liver injury. Using adoptive transfer, we demonstrate that PI3Kgamma is important not only in leukocytes but also in parenchymal cells for the progression of inflammation. We demonstrate this crosstalk between TLR9 and PI3Kgamma in vitro using human PBMCs. The inhibition of PI3Kgamma in CpG-stimulated PBMCs resulted in reduction of both cytokine production and phosphorylated Akt. Therefore, drugs that target PI3Kgamma have the potential to treat diseases mediated by excessive TLR9 signalling. |
