The small molecule inhibitor BX-795 uncouples IL-2 production from inhibition of Th2 inflammation and induces CD4⁺ T cells resembling iTreg.

ABSTRACT:

Background

Treg cells have been shown to be an important part of immune-homeostasis and IL-2 which is produced upon T cell receptor (TCR)-dependent activation of T lymphocytes has been demonstrated to critically participate in Treg development.

Objective

To evaluate small molecule inhibitors (SMI) for the identification of novel IL-2/Treg enhancing compounds.

Materials and methods

We used TCR-dependent and allergen-specific cytokine secretion of human and mouse T cells, next generation messenger ribonucleic acid sequencing (RNA-Seq) and two different models of allergic airway inflammation to examine lead SMI-compounds.

Results

We show here that the reported 3-phosphoinositide dependent kinase-1 (PDK1) SMI BX-795 increased IL-2 in culture supernatants of Jurkat

SUBMITTER: Tauber PA 

PROVIDER: S-EPMC10117943 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature