Early growth response 2 and Egr3 are unique regulators in immune system

Abstract

The immune system is evolved to defend the body against pathogens and is composed of thousands of complicated and intertwined pathways, which are highly controlled by processes such as transcription and repression of cellular genes. Sometimes the immune system malfunctions and a break down in self-tolerance occurs. This lead to the inability to distinguish between self and non-self and cause attacks on host tissues, a condition also known as autoimmunity, which can result in chronic debilitating diseases. Early growth response genes are family of transcription factors comprising of four members, Egr1, Egr2, Egr3 and Egr4. All of which contain three cyc2-His2 zinc fingers. Initially, Egr2 function was identified in the regulation of peripheral nerve myelination, hindbrain segmentation. Egr3, on the other hand, is highly expressed in muscle spindle development. Egr2 and Egr3 are induced due to the antigen stimulation and this signaling is implemented through the B and T cell receptors in the adaptive immunity. T cell receptor signaling plays a key role in Egr 2 and 3 expressions via their interaction with NFAT molecules. Egr 2 and 3 play a crucial role in regulation of the immune system and their involvement in B and T cell activation, anergy induction and preventing the autoimmune disease has been investigated. The deficiency of these transcription factors has been associated to deficient Cbl-b expression, a resistant to anergy phenotype, and expression of effector and activated T cells.

Early Growth Response Gene-2 Is Essential for M1 and M2 Macrophage Activation and Plasticity by Modulation of the Transcription Factor CEBPβ

“…Early growth response (Egr) proteins are a family of transcriptional regulators that mediate expression of multiple genes involved in cell growth and differentiation ( 16 – 18 ). There are four Egr proteins in the family and three (Egr1, Egr2, and Egr3) are expressed in macrophages ( 16 , 19 ). The exact role of Egr1, Egr2, and Egr3 in the development and function of myeloid cells, such as monocytes and macrophages, remain unclear.…”

“…Egr1, Egr2, and Egr3 expression was upregulated in myeloid progenitors when these cells are differentiated in vitro into macrophages in the presence of M-CSF ( 19 ). The role of Egr proteins was recently investigated in lymphoid cells ( 16 ); it was reported in this study that a conditional knockout for Egr2 and Egr3 resulted in a lethal autoimmune syndrome that was associated with excessive systemic levels of pro-inflammatory cytokines ( 20 ). The knockout also exhibited impaired antigen receptor-induced proliferation of B and T cells.…”

Evaluation of an angiotensin Type 1 receptor blocker on the reconsolidation of fear memory

“…This reduction in DEGs in the losartan group may suggest that post-retrieval losartan downregulates a majority of the genes that are activated during retrieval. For example, Egr2 and Egr3 , involved in neuronal plasticity and immune system activation 53 , 54 , were differentially expressed only in the saline vs. NR control group comparison, while the losartan group comparison showed differential expression for junction proteins Claudin 5 (Cldn5) and Gap junction beta-6 protein ( Gjb 6). Although speculative, this may suggest a role for peripheral losartan in modifying genes important in vascular blood brain barrier permeability, in turn impacting reconsolidation of fear memory, through an unknown mechanism.…”

Alteration of gene expression profile in CD3⁺ T-cells after downregulating MALT1

“…Numerous genetic models in mice have confirmed the essential role of various transcription factors, like NF-κB, AP1, and NFAT, in promoting T-cell activation, expansion, and effector function in response to infection. 10 – 12 In addition, abnormal pathway activation induced by TCR or abnormal activation of upstream regulators contribute to the development of autoimmunity, chronic inflammation, and malignances. 13 , 14 Moreover, T-cell-induced immune function disorders are also associated with a risk for malignant transformation.…”