REVIEW PAPER
Early growth response 2 and Egr3 are unique regulators in immune system
Submission date: 2016-05-04
Final revision date: 2016-06-28
Acceptance date: 2016-07-04
Publication date: 2017-08-08
Cent Eur J Immunol 2017;42(2):205-209
KEYWORDS
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.
REFERENCES (41)
1.
Poirier R, Cheval H, Mailhes C, et al. (2008): Distinct functions of Egr gene family members in cognitive processes. Front Neurosci 2: 47-55.
2.
Warner LE, Mancias P, Butler IJ, et al. (1998): Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nat genet 18: 382-384.
3.
Decker EL, Skerka C, Zipfel PF (1998): The Early Growth Response Protein (EGR-1) Regulates Interleukin-2 Transcription by Synergistic Interaction with the Nuclear Factor of Activated T Cells. J Biol Chem 273: 26923-26930.
4.
Bettini M, Xi H, Milbrandt J, Kersh GJ (2002): Thymocyte Development in Early Growth Response Gene 1-Deficient Mice. J Immunol 169: 1713-1720.
5.
Rivera RR, Johns CP, Quan J, et al. (2000): Thymocyte selection is regulated by the helix-loop-helix inhibitor protein, Id3. Immunity 12: 17-26.
6.
Bain G, Cravatt CB, Loomans C, et al. (2001): Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade. Nat Immunol 2: 165-171.
7.
Krishnaraju K, Nguyen HQ, Liebermann DA, Hoffman B (1995): The Zinc Finger Transcription Factor Egr-1 Potentiates Macrophage Differentiation of Hematopoietic cells. Mol Cell Biol 15: 5499-5507.
8.
O’donovan KJ, Tourtellotte WG, Milbrandt J, Baraban J M (1999): The Egr family of transcription-regulatory factors: Progress at the interface of molecular and systems neuroscience. Trends Neurosci 22: 167-173.
9.
Tourtellotte WG, Nagarajan R, Auyeung A, et al. (1999): Infertility associated with incomplete spermatogenic arrest and oligozoospermia in Egr4-deficient mice. Development 126: 5061-5071.
10.
Bae CJ, Jeong J, Saint-Jeannet JP (2015): A novel function for Egr4 in posterior hindbrain development. Sci Rep 5: 7750.
11.
Li S, Symonds AL, Zhu B, et al. (2011): Early growth response gene-2 (Egr-2) regulates the development of B and T cells. PLoS One 6: e18498.
12.
Germain RN (2002): T-cell development and the CD4-CD8 lineage decision. Nat Rev Immunol 2: 309-322.
13.
Li S, Miao T, Sebastian M, et al. (2012): The transcription factors Egr2 and Egr3 are essential for the control of inflammation and antigen-induced proliferation of B and T cells. Immunity 37: 685-696.
14.
Lemaire P, Revelant O, Bravo R, Charnay P (1998): Two mouse genes encoding potential transcription factors with identical DNA-binding domains are activated by growth factors in cultured cells. Proc Natl Acad Sci 85: 4691-4695.
15.
Unoki M, Nakamura Y (2001): Growth-sppressive effects of BPOZ and EGR2, two genes involved in hte PTEN signaling pathway. Oncogene 20: 4457-4465.
16.
Unoki M, Nakamura Y (2003): EGR2 induces apoptosis in various cancer cell lines by direct transactivation of BNIP3L and BAK. Oncogene 22: 2172-2185.
17.
Salotti J, Sakchaisri K, Tourtellotte WG, Johnson PF (2015): An Arf-Egr-C/EBP beta pathway linked to ras-induced senescence and cancer. Mol Cell Biol 35: 866-883.
18.
Gabet Y, Baniwal SK, Leclerc N, et al. (2010): Krox20/EGR2 deficiency accelerates cell growth and differentiation in the monocytic lineage and decreases bone mass. Blood 116: 3964-3971.
19.
Parkinson DB, Bhaskaran A, Droggiti A, et al. (2004): Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death. J Cell Biol 164: 385-394.
20.
Grunewald TG, Bernard V, Gilardi-Hebenstreit P, et al. 2015. Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite. Nat Genet 47: 1073-1078.
22.
Hargreaves RG, Borthwick NJ, Gilardini Montani MS, et al. (1997): Dissociation of T cell anergy from apoptosis by blockade of Fas/Apo-1 (CD95) signaling. J Immunol 158: 3099-3107.
23.
Zheng Y, Zha Y, Spaapen RM, et al. (2013): Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic targets in T cell anergy. Mol immunol 55: 283-291.
24.
Zheng Y, Zha Y, Driessens G, et al. (2012): Transcriptional regulator early growth response gene 2 (Egr2) is required for T cell anergy in vitro and in vivo. J Exp Med 209: 2157-2163.
25.
Collins S, Lutz MA, Zarek PE, et al. (2008): Opposing regulation of T cell function by Egr-1/NAB2 and Egr-2/Egr-3. Eur J Immunol 38: 528-536.
26.
Collins S, Wolfraim LA, Drake CG, et al. (2006): Cutting Edge: TCR-Induced NAB2 Enhances T Cell Function by Coactivating IL-2 Transcription. J Immunol 177: 8301-8305.
27.
Safford M, Collins S, Lutz MA, et al. (2005): Egr-2 and Egr-3 are negative regulators of T cell activation. Nat Immunol 6: 472-480.
28.
Harris JE, Bishop KD, Phillips NE, et al. (2004): Early Growth Response Gene-2, a Zinc-Finger Transcription Factor, Is Required for Full Induction of Clonal Anergy in CD4+ T Cells. J Immunol 173: 7331-7338.
29.
Oh Y M, Park HB, Shin JH, et al. (2015): Ndrg1 is a T-cell clonal anergy factor negatively regulated by CD28 costimulation and interleukin-2. Nat Commun 6: 8698.
30.
Noah TA, Weil ZM, Nelson RJ (2012): Inflammation: Mechanisms, Costs, and Natural Variation. Annu Rev Ecol Sys 43, 385-406.
32.
Sumitomo S, Fujio K, Okamura T, Yamamoto K (2013): Egr2 and Egr3 are the unique regulators for systemic autoimmunity. JAKSTAT 2: e23952.
33.
Chong MM, Metcalf D, Jamieson E, et al. (2005): Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation. Blood 106: 1668-1675.
34.
Croker BA, Metcalf D, Robb L, et al. (2004): SOCS3 Is a Critical Physiological Negative Regulator of G-CSF Signaling and Emergency Granulopoiesis. Immunity 20: 153-165.
35.
Ramgolam VS, Markovic-Plese S. (2011): Regulation of suppressors of cytokine signaling as a therapeutic approach in autoimmune diseases, with an emphasis on multiple sclerosis. J Signal Transduct 2011: 635721.
36.
Miao T, Raymond M, Bhullar P, et al. (2012): Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf. J Immunol 190: 58-65.
37.
Zhu B, Symonds ALJ, Martin JE, et al. (2008): Early growth response gene 2 (Egr-2) controls the self-tolerance of T cells and prevents the development of lupuslike autoimmune disease. J Exp Med 205: 2295-2307.
38.
Schumann J, Stanko K, Schliesser U, et al. (2015): Differences in CD44 Surface Expression Levels and Function Discriminates IL-17 and IFN-gamma Producing Helper T Cells. PLoS One 10: e0132479.
39.
Crispin JC, Oukka M, Bayliss G, et al. (2008): Expanded Double Negative T Cells in Patients with Systemic Lupus Erythematosus Produce IL-17 and Infiltrate the Kidneys. J Immunol 181: 8761-8766.
40.
Sela U, Dayan M, Hershkoviz R, et al. (2008): A Peptide That Ameliorates Lupus Up-Regulates the Diminished Expression of Early Growth Response Factors 2 and 3. J Immunol 180: 1584-1591.
41.
Kane LP, Weiss A. (2003): The PI-3 Kinase/Akt pathway and T cell activation: Pleiotropic pathways downstream of PIP3. Immunol Rev 12: 7-20.
Share
RELATED ARTICLE
| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
