mafB在細胞激素調節上所扮演的角色

Abstract

細胞激素 (cytokine)在許多之前研究中已經被指出能夠決定輔助型T細胞 (T helper cell)分化的命運。第一類輔助型T細胞 (Th1 cell)會分泌第一類細胞激素，例如干擾素γ(IFN-γ)；而第二類輔助型T細胞(Th2 cell)則會分泌第二類細胞激素，例如：介白素4(IL- 4)、介白素5 (IL-5)、介白素10 (IL-10)及介白素13 (IL-13)。這些細胞激素能分別促進更多未分化的輔助型T細胞分化成第一類或第二類輔助型T細胞。在輔助型T細胞中，c-Maf專一地扮演著調控介白素4表現的轉錄因子 (transcription factor)的角色。當第二類輔助型T細胞活化時，會表現更多介白素4，因而促進更多第二類輔助型T細胞的分化。當c-Maf在輔助型T細胞的表現有缺陷時，則會導致輔助型T細胞朝向第一類輔助型T細胞的型態發展，也因此加劇許多由第一類輔助型T細胞所導致的疾病，例如：自體免疫性糖尿病 (antoimmune diabetes)。在此，我們發現另一個Maf蛋白家族的成員－MafB，在經過in vitro活化後之in vitro或in vivo 培養的 EL4細胞株中皆有顯著的表現。此外，在活化之後，MafB的表現量在趨向第一類輔助型T細胞型態的CD4＋T細胞中會降低，而在趨向第二類輔助型T細胞型態的CD4＋T細胞中則明顯地升高。由我們的螢光素酶分析實驗 (luciferase analysis)所得到的資料中也發現，MafB和c-Maf一樣能夠顯著地增加介白素2 (IL-2)、介白素4、介白素5、介白素10、介白素12 (IL-12)及介白素13啟動子 (promoter)的活性，但對於干擾素

Cytokines have been demonstrated to determine the cell fate during T helper cell differentiation. Th1 and Th2 cells separately secrete Th1 cytokine, such as IFN-γ, and Th2 cytokines, such as IL-4, IL-5, IL-10 and IL-13, and thereby promote more naïve T helper cells to differentiate into Th1 or Th2 cells. c-Maf is an IL-4-specific transcription factor in T helper cells. Upon stimulation, c-Maf is highly upregulated in Th2 cells, and can induce significant IL-4 expression to promote Th2 cell differentiation. T helper cells deficient in c-Maf result in a spontaneous bias toward the Th1 phenotype, which favors Th1-mediated diseases, such as autoimmune diabetes. Here, we demonstrate that another Maf family protein, MafB, is expressed both in in vitro- and in vivo-passaged EL4 cells upon stimulation in vitro. Moreover, the expression of MafB is downregulated in Th1-skewed CD4+ T cells, whereas it is obviously upregulated in Th2-skewed CD4+ T cells after activation. In consistent with c-Maf, MafB can significantly transactivate the activity on IL-2, IL-4, IL-5, IL-10, IL-12 and IL-13 promoters, but not on IFN-γ promoter, according to our luciferase analysis. Furthermore, CD4+ T helper cells overexpressing mafB or c-maf, through retroviral transduction, also show higher expressions of IL-4, IL-5, IL-10 and IL-13. Since MafB shows similar effects to c-Maf on cytokine regulation, an overlapping role of MafB and c-Maf in Th2 cell differentiation is suggested. However, the role of MafB in cytokine regulation and Th2 cell differentiation needs more investigation.