TGF-β1 expression in regulatory NK1.1-CD4+NKG2D+ T cells dependents on the PI3K-p85α/JNK, NF-κB and STAT3 pathways.

ABSTRACT: NK1.1-CD4+NKG2D+ cells exert their immune-regulatory function in tumor as an unconventional regulatory T cell subset through the production of TGF-β1; however, the molecular mechanisms involving with the activation of nuclear factors for TGF-β1 transcription remain unclear. Here we determined that the PI3K-p85α subunit was specifically activated in NK1.1-CD4+NKG2D+ cells following an 8-hour stimulation by sRAE-1 or α-CD3/sRAE-1, subsequently leading to the activation of PI3K-p110, Akt, and JNK. On the contrary, α-CD3/α-CD28 stimulation did not induce the activation of PI3K-p85 and JNK. Consequently, activation of the nuclear transcription factor AP-1 as a consequence of JNK activation regulated TGF-β1 expression in NK1.1-CD4+NKG2D+ cells. Furthermore, activation of NF-κB in NK1.1-CD4+NKG2D

SUBMITTER: Han S 

PROVIDER: S-EPMC5883098 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature