ArticleJCI insight2025
BLIMP-1 and CEACAM1 cooperatively regulate human Treg homeostasis and function to control xenogeneic GVHD.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Dual-recognizing antibodies targeting CEACAMs in the tumor microenvironment: towards more precise targeting.Cell communication and signaling : CCS · 2026Review
- The Heteromeric Dopamine Receptor D2:D3 Controls the Gut Recruitment and Suppressive Activity of Regulatory T-Cells.International journal of molecular sciences · 2025Article
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Authors and funding
13 authors.
Funding
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 responsiveness to CD3/CD28 signaling and activation of mTOR. Prolonged IL-2R signaling optimizes BLIMP-1 expression, supporting chromosomal opening of CEACAM1 to increased CEACAM1 expression through STAT5- and BLIMP-1-driven enhancers. Correspondingly, CEACAM1 is highly induced on Tregs from patients with autoimmune disease undergoing low-dose IL-2 therapy, and these Tregs showed reduced proliferation. A humanized mouse model of xenogeneic graft-versus-host disease demonstrates that BLIMP-1 normally promotes, while CEACAM1 restrains, Treg suppressive activity. Collectively, our findings reveal that BLIMP-1 and CEACAM1 function in an IL-2-dependent feedback loop to restrain Treg proliferation and affect suppressive function. CEACAM1 also acts as a highly selective biomarker of IL-2R signaling in human T cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.