Sherman M A, Secor V H, Lee S K, Lopez R D, Brown M A
Department of Pathology, Emory University, Atlanta, GA 30322, USA.
Eur J Immunol. 1999 Apr;29(4):1235-42. doi: 10.1002/(SICI)1521-4141(199904)29:04<1235::AID-IMMU1235>3.0.CO;2-0.
The acquisition of an IL-4-producing phenotype in Th2 cells requires IL-4 signaling through the STAT6 pathway during T cell differentiation. In this study we demonstrate that, unlike in naive T cells, IL-4 is not necessary for the development of an IL-4-producing phenotype in mast cells. Bone marrow-derived mast cell precursors from STAT6-/- mice can differentiate into mature cells that express IL-4 levels comparable to those of wild-type mast cells. In differentiated mast cells, activation in the presence of neutralizing anti-IL-4 antibodies or mutation of the consensus STAT6 sites does not diminish IL-4 promoter activity, indicating that IL-4 is not required for active transcription. Taken together, these data suggest that mast cell IL-4 production is not STAT6 dependent, providing evidence that these cells could generate IL-4 needed for the initiation and amplification of an effective Th2 immune response.
在T细胞分化过程中，Th2细胞获得产生白细胞介素4（IL-4）的表型需要通过信号转导和转录激活因子6（STAT6）途径进行IL-4信号传导。在本研究中，我们证明，与初始T细胞不同，IL-4对于肥大细胞中产生IL-4的表型的发育并非必需。来自STAT6基因敲除小鼠的骨髓源性肥大细胞前体可以分化为成熟细胞，其表达的IL-4水平与野生型肥大细胞相当。在分化的肥大细胞中，在存在中和性抗IL-4抗体的情况下激活或共有STAT6位点发生突变，并不会降低IL-4启动子活性，这表明活性转录不需要IL-4。综上所述，这些数据表明肥大细胞产生IL-4不依赖于STAT6，这为这些细胞能够产生启动和放大有效的Th2免疫反应所需的IL-4提供了证据。
