Blimp-1 Induced by IL-4 Plays a Critical Role in Suppressing IL-2 Production in Activated CD4 T Cells

Wang, Lu; Panhuys, Nicholas J. Van; Hu‐Li, Jane; Kim, Sohee; Gros, Graham Le; Min, Booki

doi:10.4049/jimmunol.181.8.5249

Cited by 18 publications

(16 citation statements)

References 47 publications

(65 reference statements)

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“…JunB , whose expression is selectively upregulated in Th2 cells, collaborates with c-Maf in inducing IL-4 production through binding to the Il4 promoter (170). Expression of Blimp-1, an important transcription factor for long-lived plasma cells, is induced in Th2 cells where it suppresses IFN-γ and IL-2 production (171–173). Blimp-1 has recently been reported to oppose the expression of Bcl-6 and thus to inhibit Tfh differentiation (101).…”

Section: Transcription Factors For T Helper Cell Fate Determinationmentioning

confidence: 99%

Differentiation of Effector CD4 T Cell Populations

Zhu

Yamane

Paul

2010

Annu. Rev. Immunol.

2,891

2,823

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CD4 T cells play critical roles in mediating adaptive immunity to a variety of pathogens. They are also involved in autoimmunity, asthma, and allergic responses as well as in tumor immunity. During TCR activation in a particular cytokine milieu, naive CD4 T cells may differentiate into one of several lineages of T helper (Th) cells, including Th1, Th2, Th17, and iTreg, as defined by their pattern of cytokine production and function. In this review, we summarize the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.

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Section: Transcription Factors For T Helper Cell Fate Determinationmentioning

confidence: 99%

Differentiation of Effector CD4 T Cell Populations

Zhu

Yamane

Paul

2010

Annu. Rev. Immunol.

2,891

2,823

View full text Add to dashboard Cite

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“…Blimp-1 attenuates IFN-γ production in CD4 + T cells activated in vitro under nonpolarizing conditions and in vivo [11, 35, 38]. Wang et al showed that Blimp-1 is very strongly induced and plays a role in IL-2 inhibition when naive T cells are stimulated in the presence of IL-4, both in vitro and in vivo [46]. IL-2 is critical for T cell immunity to promote proliferation, activation and differentiation of T cells [47]; it induces Blimp-1 expression in activated T cells and inhibits its own production through the induction of Blimp-1 in a negative feedback loop [15, 16].…”

Section: The Effects Of Blimp-1 On T Cell Functionsmentioning

confidence: 99%

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

Yeh

Chu

et al. 2017

J Biomed Sci

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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.

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“…In the absence of Blimp-1, mice develop a lethal multiorgan inflammatory disease caused by an accumulation of effector and memory T cells (116), thus making Blimp-1 an important regulator of the adaptive immune response. Blimp-1 is also required for repression of Il2 transcription in T cells, resulting in an autoregulatory loop that controls immune responses (117, 118). In addition, Blimp-1 is crucial for the IL-27-dependent induction of IL-10 by Th1 cells (so-called Tr1 cells) following infection with Toxoplasma gondii or influenza A virus (119, 120).…”

Section: Interactions and Potential Roles Of G9amentioning

confidence: 99%

The Lysine Methyltransferase G9a in Immune Cell Differentiation and Function

Scheer

Zaph

2017

Front. Immunol.

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G9a (KMT1C, EHMT2) is a lysine methyltransferase (KMT) whose primary function is to di-methylate lysine 9 of histone H3 (H3K9me2). G9a-dependent H3K9me2 is associated with gene silencing and acts primarily through the recruitment of H3K9me2-binding proteins that prevent transcriptional activation. Gene repression via G9a-dependent H3K9me2 is critically required in embryonic stem (ES) cells for the development of cellular lineages by repressing expression of pluripotency factors. In the immune system, lymphoid cells such as T cells and innate lymphoid cells (ILCs) can differentiate from a naïve state into one of several effector lineages that require both activating and repressive mechanisms to maintain the correct gene expression program. Furthermore, the long-term immunity to re-infection is mediated by memory T cells, which also require specific gene expression and repression to maintain a quiescent state. In this review, we examine the molecular machinery of G9a-dependent functions, address the role of G9a in lymphoid cell differentiation and function, and identify potential functions of T cells and ILCs that may be controlled by G9a. Together, this review will highlight the dynamic nature of G9a-dependent H3K9me2 in the immune system and shed light on the nature of repressive epigenetic modifications in cellular lineage choice.

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Blimp-1 Induced by IL-4 Plays a Critical Role in Suppressing IL-2 Production in Activated CD4 T Cells

Cited by 18 publications

References 47 publications

Differentiation of Effector CD4 T Cell Populations

Differentiation of Effector CD4 T Cell Populations

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

The Lysine Methyltransferase G9a in Immune Cell Differentiation and Function

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