New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function

Abstract

B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3+ regulatory T cells with an effector phenotype. Blimp-1 is also required to induce cell elimination in the thymus and critically modulates peripheral T cell activation and proliferation. In addition, Blimp-1 promotes T helper (Th) 2 lineage commitment and limits Th1, Th17 and follicular helper T cell differentiation. Furthermore, Blimp-1 coordinates with other transcription factors to regulate expression of IL-2, IL-21 and IL-10 in effector T lymphocytes. In CD8+ T cells, Blimp-1 expression is distinct in heterogeneous populations at the stages of clonal expansion, differentiation, contraction and memory formation when they encounter antigens. Moreover, Blimp-1 plays a fundamental role in coordinating cytokine receptor signaling networks and transcriptional programs to regulate diverse aspects of the formation and function of effector and memory CD8+ T cells and their exhaustion. Blimp-1 also functions as a gatekeeper of T cell activation and suppression to prevent or dampen autoimmune disease, antiviral responses and antitumor immunity. In this review, we discuss the emerging roles of Blimp-1 in the complex regulation of gene networks that regulate the destiny and effector function of T cells and provide a Blimp-1-dominated transcriptional framework for T lymphocyte homeostasis.

Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia

“…Although Blimp-1 was previously indicated to be involved in Th cell differentiation (43), the present results indicate a remarkable change in the Bcl-6 gene levels and did not demonstrate a significant change of Blimp-1 levels at transcription level in cITP patients.…”

An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells

“…In humans, increased frequency of EOMES positive CD8 T-cells is present in the effector populations 9 , 10 . In CD8 T-cells, PRDM1/BLIMP1 is essential for optimal effector functions including effector cell migration and granzyme production 11 – 13 . Importantly, expression of two key transcription factors that are required for a long-term functional memory formation, TCF7 and LEF1 14 , 15 , was significantly downregulated in SIRPγ low CD8 T-cells from CT carriers (Fig.…”

CD4+T Cell Subsets and Pathways to HIV Latency

“…These transcription factors are directly involved in the differentiation of effector T follicular helper cells (T FH ) and T memory subsets. [107][108][109][110][111] High Bcl6 expression and low Blimp-1 expression support T FH differentiation, whereas, elevated Blimp-1 expression is observed in quiescent memory T cell subsets. Both of these factors have been shown to directly and indirectly regulate HIV replication.…”