BLIMP1 negatively regulates IL-2 signaling in T cells
- Suyasha Roy
- Min Ren
- Peng Li
- Kairong Cui
- Yaqiang Cao
- Bryan Fisk
- Tovah E. Markowitz
- Neelam Redekar
- Keiko Sakamoto
- Keisuke Nagao
- Jangsuk Oh
- Rosanne Spolski
- Wei Liao
- Sigrid P. Dubois
- Brian L. Kelsall
- Keji Zhao
- James D. Phelan
- Warren J. Leonard
2025-07-18
Interleukin-2 (IL-2) regulates immune homeostasis by fine-tuning the balance between effector and regulatory T (T reg ) cells. To identify regulators of IL-2 signaling, we performed genome-wide CRISPR-knockout screening in IL-2–dependent cells derived from a patient with adult T cell leukemia (ATL) and found enrichment of single guide RNAs targeting PRDM1 , which encodes B lymphocyte–induced maturation protein 1 (BLIMP1). BLIMP1 inhibits IL-2 production by T cells; however, its role in IL-2 signaling remains unknown. Here, we show that overexpressing Prdm1 down-regulated IL-2 signaling, whereas Prdm1 -deficiency enhanced IL-2 signaling in mouse CD4 + T cells and T reg cells with augmented IL-2 signaling in T cells from influenza-infected mice and during adoptive T cell transfer–induced colitis. Deleting PRDM1 in human CD4 + T cells and T reg cells also increased IL-2 signaling. Furthermore, CD4 + T cells from patients with ATL expressed less BLIMP1 and had enhanced IL-2 signaling, whereas overexpressing PRDM1 in ATL cells suppressed IL-2 signaling. Thus, BLIMP1 inhibits IL-2 signaling during normal and pathophysiological responses, suggesting that manipulating BLIMP1 could have therapeutic potential.