GlyT1 inhibition by ALX-5407 attenuates allograft rejection through suppression of Th1 cell differentiation.

ABSTRACT:

Objective

Transplant rejection driven by Th1 cell-mediated immune responses remains a critical challenge. This study aimed to investigate the role of glycine transporter 1 (GlyT1/SLC6A9) in Th1 differentiation and evaluate the therapeutic potential of its inhibitor, ALX-5407, in attenuating allograft rejection.

Methods

RNA sequencing, flow cytometry, and qRT-PCR were employed to analyze GlyT1 expression in Th1-polarized CD4⁺T cells. ALX-5407 (0.5-500 nM) was tested in vitro under Th1-polarizing conditions. A murine skin allograft model (BALB/c to C57BL/6) was established to assess graft survival and immune responses. Combination therapy with rapamycin and ALX-5407 was evaluated through histopathology, immunofluorescence, and splenocyte profiling. Mechanisti

SUBMITTER: Zhang X 

PROVIDER: S-EPMC12500449 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature