Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ

DSpace/Manakin Repository

Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ

Citable link to this page


Title: Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ
Author: Uehara, Mayuko; McGrath, Martina M.; Ohori, Shunsuke; Solhjou, Zhabiz; Banouni, Naima; Routray, Sujit; Evans, Catherine; DiNitto, Jonathan P.; Elkhal, Abdallah; Turka, Laurence A.; Strom, Terry B.; Tullius, Stefan G.; Winkler, David G.; Azzi, Jamil; Abdi, Reza

Note: Order does not necessarily reflect citation order of authors.

Citation: Uehara, M., M. M. McGrath, S. Ohori, Z. Solhjou, N. Banouni, S. Routray, C. Evans, et al. 2017. “Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ.” Nature Communications 8 (1): 951. doi:10.1038/s41467-017-00982-x.
Full Text & Related Files:
Abstract: Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defects in these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ and PI3Kδ on alloimmunity remain underexplored. Here, we show that both PI3Kγ −/− and PI3Kδ D910A/D910A mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection. However, PI3Kδ mutation also dampens regulatory T cells (Treg). After treatment with low dose CTLA4-Ig, PI3Kγ −/−, but not PI3Κδ D910A/D910A, recipients exhibit indefinite prolongation of heart allograft survival. PI3Kδ D910A/D910A Tregs have increased apoptosis and impaired survival. Selective inhibition of PI3Kγ and PI3Kδ (using PI3Kδ and dual PI3Kγδ chemical inhibitors) shows that PI3Kγ inhibition compensates for the negative effect of PI3Kδ inhibition on long-term allograft survival. These data serve as a basis for future PI3K-based immune therapies for transplantation.
Published Version: doi:10.1038/s41467-017-00982-x
Other Sources:
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at
Citable link to this page:
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search