| First Author | Roller A | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 9 | Pages | 4612-20 |
| PubMed ID | 23024273 | Mgi Jnum | J:190607 |
| Mgi Id | MGI:5449294 | Doi | 10.4049/jimmunol.1103173 |
| Citation | Roller A, et al. (2012) Blockade of phosphatidylinositol 3-kinase (PI3K)delta or PI3Kgamma reduces IL-17 and ameliorates imiquimod-induced psoriasis-like dermatitis. J Immunol 189(9):4612-20 |
| abstractText | Psoriasis is a chronic inflammatory skin disease triggered by interplay between immune mediators from both innate and adaptive immune systems and skin tissue, in which the IL-23/IL-17 axis is critical. PI3Kdelta and PI3Kgamma play important roles in various immune cell functions. We found that mice lacking functional PI3Kdelta or PI3Kgamma are largely protected from imiquimod (IMQ)-induced psoriasis-like dermatitis, correlating with reduced IL-17 levels in the lesions, serum, and the draining lymph nodes. TCRgammadelta T cells were the major IL-17-producing population in the draining lymph nodes and were significantly diminished in IMQ-treated PI3Kdelta knockin and PI3Kgamma knockout mice. We also show that PI3Kdelta and PI3Kgamma inhibitors reduced IFN-gamma production by human TCRgammadelta T cells and IL-17 and IFN-gamma production by PBMCs from psoriatic or healthy donors. In addition, inhibition of PI3Kgamma, but not PI3Kdelta, blocked chemotaxis of CCR6(+)IL-17-producing cells from IMQ-treated mice or healthy human donors. Taken together, these data indicate that PI3Kdelta and/or PI3Kgamma inhibitors should be considered for treating IL-17-driven diseases, such as psoriasis. |
