Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4⁺ T Cell Dysfunction.

ABSTRACT: CD4⁺ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4⁺ T cell dysfunction and long-term allograft survival. Mechanistically, IRF4 repressed PD-1, Helios, and other molecules associated with T cell dysfunction. In the absence of IRF4, chromatin accessibility and binding of Helios at PD-1 cis-regulatory elements were increased, resulting in enhanced PD-1 expression and CD4⁺ T cell dysfunction. The dysfunctional state of Irf4-de

SUBMITTER: Wu J 

PROVIDER: S-EPMC5759774 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature