BLIMP-1 and CEACAM1 cooperatively regulate human Treg homeostasis and function to control xenogeneic GVHD.

ABSTRACT: Regulatory T cells (Tregs) are essential for peripheral tolerance and depend on TCR and IL-2 receptor (IL-2R) signaling for their homeostasis and function. In mice, IL-2-dependent B-lymphocyte-induced maturation protein 1 (BLIMP-1) contributes to Treg homeostasis. BLIMP-1 is a major transcriptional hub in human Tregs, but its mechanisms of action remain undefined. Here, using CRISPR/Cas9 ablation, we show that BLIMP-1 limits human Treg proliferation but supports IL-10, cytotoxic T lymphocyte-associated protein 4, several immune checkpoints including carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and Treg functional activity. BLIMP-1 restrains Treg expansion to IL-2 by downregulating CD25 and IL-2R signaling, and by enhancing CEACAM1 expression, which in turn inhibits

SUBMITTER: Ding Y 

PROVIDER: S-EPMC12487853 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature