Background
EBI3 (Epstein-Barr virus Induced-3) is a secreted glycoprotein of the hematopoietin receptor family. It plays a critical regulatory role in the induction of Th2-type immune responses and the development of Th2-mediated tissue inflammation in vivo, which may be mediated through the control of iNKT cell function. EBI3 dimerizes with p28 and p35 subunits of IL-12 to form new proteins IL-27 and IL-35, respectively (Honglian Tong et al, 2010). IL-27 is an early product of activated antigen presenting cell that is produced upon TLR ligation. It negatively regulates Th17 cell differentiation. EBI3 is widely expressed and its expression in dendritic cell is transcriptionally regulated by TLR signaling via MyD88 and NF-kappaB during innate immune responses preceding cytokine driven Th cell development. EBI3 signal inhibits delayed-type hypersensitivity responses by suppressing IL-17 production and inducing IL-10 hyperproduction. EBI3 may play a novel role in controlling tumor metastasis via lung CD8+ T cells, and its deficiency is associated with a diminished production of Th2 cytokines which are known to regulate allergic airway inflammation in asthma. Targeted deletion of EBI3 protects mice from lung metastasis (Kerstin A et al, 2008). |
Reference
1. Wirtz S, Becker C, Fantini M, Nieuwenhuis E, Tubbe I, Galle P, Schild H, Birkenbach M, Blumberg R, Neurath M. EBV-Induced Gene 3 Transcription Is Induced by TLR Signaling in Primary Dendritic Cells via NF-kB Activiation. J Immunol. 2005 174; 2814-2824.
2. Sauer KA, Maxeiner JH, Karwot R, Scholtes P, Lehr HA, Birkenbach M, Blumberg RS, Finotto S. Immunosurveillance of lung melanoma metastasis in EBI-3-deficient mice mediated by CD8+ T cells. J Immunol. 2008 Nov 1;181(9):6148-57. PMID: 18941205
3. Tong H, Miyazaki Y, Yamazaki M, Hara H, Waldmann H, Hori S, Yoshida H. Exacerbation of delayed-type hypersensitivity responses in EBV-induced gene-3 (EBI-3)-deficient mice. Immunol Lett. 2010 Feb 16;128(2):108-15. Epub 2010 Jan 12. PMID: 20064562
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