The Role of the Transcription Factor CREB in Immune Function

Abstract

CREB is a transcription factor that regulates diverse cellular responses, including proliferation, survival, and differentiation. CREB is induced by a variety of growth factors and inflammatory signals and subsequently mediates the transcription of genes containing a cAMP-responsive element. Several immune-related genes possess this cAMP-responsive element, including IL-2, IL-6, IL-10, and TNF-α. In addition, phosphorylated CREB has been proposed to directly inhibit NF-κB activation by blocking the binding of CREB binding protein to the NF-κB complex, thereby limiting proinflammatory responses. CREB also induces an antiapoptotic survival signal in monocytes and macrophages. In T and B cells, CREB activation promotes proliferation and survival and differentially regulates Th1, Th2, and Th17 responses. Finally, CREB activation is required for the generation and maintenance of regulatory T cells. This review summarizes current advances involving CREB in immune function—a role that is continually being defined.

Mechanisms of Rapid Induction of Interleukin-22 in Activated T Cells and Its Modulation by Cyclosporin A

“…The present observation of CREB being a significant determinant of IL-22 expression agrees with the view that this transcription factor promotes diverse aspects of T cell activation and proliferation, among others, production of IL-2 and IFN␥ as well as Th1-directed immunity in general (46). In this context, it is noteworthy that IL-22 has been identified as part of the Th1 cytokine response early on (3).…”

“…ble in T/A-stimulated Jurkat T cells (Fig. 4A), an observation agreeing with activation of this transcription factor by PKC (46). T/A-mediated physical binding of CREB to this particular CRE in the IL22 promoter was confirmed by ChIP (Fig.…”

“…2) with an unusual imperfect nucleotide sequence (46). In fact, phosphorylated nuclear CREB became detecta-FIGURE 2.…”

The microRNA-212/132 cluster regulates B cell development by targeting Sox4

“…This highlights a potentially unique regulation of miR-212/132 in B cells, independent of what has been observed in macrophages, where a significant, but less dramatic induction of miR-212/132 has been observed with TLR4 stimulation (Taganov et al, 2006;Shaked et al, 2009). Importantly, this induction was replicated by stimulation with PMA, a DAG analogue, but not with ionomycin, which mimics Ca 2+ influx into a cell, thus suggesting that miR-212/132 may be regulated by CREB or a host of other factors in B cells, as has been observed in neurons (Klein et al, 2007;Wen et al, 2010). nodes ( Fig.…”

Adenosine Production by Biomaterial‐Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury

“…Activation of the adenosine A2a‐receptor signaling pathway is implicated in phosphorylation of cyclic‐AMP responsive element‐binding protein, which in turn inhibits nuclear factor‐κβ through competitive binding at DNA transcriptional promoter sites 63. Competitive inhibition of nuclear factor‐κβ by cyclic‐AMP responsive element‐binding protein is known as 1 important downstream mechanism for disrupting activation of innate immunity 64. Alternatively, the A2b receptor has also been implicated for its role in ischemic preconditioning in a mouse model of MI/R, suggesting that CD73‐mediated adenosine production by MSCs could act on a number of downstream targets 65…”