| First Author | Barbera Betancourt A | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 1 | Pages | e0146516 |
| PubMed ID | 26783747 | Mgi Jnum | J:240094 |
| Mgi Id | MGI:5882310 | Doi | 10.1371/journal.pone.0146516 |
| Citation | Barbera Betancourt A, et al. (2016) Inhibition of Phosphoinositide 3-Kinase p110delta Does Not Affect T Cell Driven Development of Type 1 Diabetes Despite Significant Effects on Cytokine Production. PLoS One 11(1):e0146516 |
| abstractText | Type 1 diabetes is caused by the destruction of insulin producing beta cells by the immune system. The p110delta isoform of PI3K is expressed primarily in cells of haematopoietic origin and the catalytic activity of p110delta is important for the activation of these cells. Targeting of this pathway offers an opportunity to reduce immune cell activity without unwanted side effects. We have explored the effects of a specific p110delta isoform inhibitor, IC87114, on diabetogenic T cells both in vitro and in vivo, and find that although pharmacological inhibition of p110delta has a considerable impact on the production of pro-inflammatory cytokines, it does not delay the onset of diabetes after adoptive transfer of diabetogenic cells. Further, we demonstrate that combination treatment with CTLA4-Ig does not improve the efficacy of treatment, but instead attenuates the protective effects seen with CTLA4-Ig treatment alone. Our results suggest that decreased IL-10 production by Foxp3+ CD4+ T cells in the presence of IC87114 negates individual anti-inflammatory effects of IC8114 and CTLA4-Ig. |
