| First Author | Ji H | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 8 | Pages | 2940-7 |
| PubMed ID | 17626838 | Mgi Jnum | J:143141 |
| Mgi Id | MGI:3822972 | Doi | 10.1182/blood-2007-04-086751 |
| Citation | Ji H, et al. (2007) Inactivation of PI3Kgamma and PI3Kdelta distorts T-cell development and causes multiple organ inflammation. Blood 110(8):2940-7 |
| abstractText | Mice lacking both the p110gamma and p110delta isoforms display severe impairment of thymocyte development. Here, we show that this phenotype is recapitulated in p110gamma-/-/p110delta(D910A/D910A) (p110gamma(KO)delta(D910A)) mice where the p110delta isoform has been inactivated by a point mutation. Moreover, we have examined the pathological consequences of the p110gammadelta deficiency, which include profound T-cell lymphopenia, T-cell and eosinophil infiltration of mucosal organs, elevated IgE levels, and a skewing toward Th2 immune responses. Using small-molecule selective inhibitors, we demonstrated that in mature T cells, p110delta, but not p110gamma, controls Th1 and Th2 cytokine secretion. Thus, the pathology in the p110gammadelta-deficient mice is likely to be secondary to a developmental block in the thymus that leads to lymphopenia-associated inflammatory responses. |
