TGF-β参与IL-18刺激Th1型细胞分泌IL-9

发布时间：2019-06-07 17:14

【摘要】：最近的报告发现的CD4+Th细胞亚群,在特定的细胞因子环境下,有能力改变他们的基因表达模式。我们之前发现Thl细胞在受到抗原OVA,IL-2和IL-18刺激下可以产生IL-3,IL-9,IL-13和粒细胞巨噬细胞集落刺激因子GM-CSF,基于其独特的Thl细胞的可塑性特点,我们将这一类活化的Thl细胞命名为“超级Thl细胞”(Super Thl cells)。在这篇论文中,我们采用流式细胞分选技术分离提取小鼠原代naive CD4+T细胞,将其分化至成熟的Thl细胞,给予IL-18和TCR再刺激后,利用流式细胞分析技术,酶联免疫吸附实验,RT-PCR等手段观察Thl表型的改变。我们首次发现IL-18和T细胞受体的刺激可以使分化成熟Thl细胞分泌更多的TGF-β,这些TGF-β对于T细胞调控起到了关键作用,因为它们参与了Super Th1细胞分泌IL-9的过程。此外,将分化成熟的Thl细胞给予CD3抗体刺激后,我们发现Thl细胞会同时分泌少量的IL-4,这些IL-4和TGF-β协同起来促使Thl细胞分泌大量的IL-9。同时,IL-4/STAT6信号通路也是IL-9得以大量表达的必要条件。总之,在本篇论文中,我们首次发现并论证了在Super Thl细胞合成IL-9的过程中,TGF-β发挥着极为关键的作用。Thl细胞在IL-18和TCR的共同刺激条件下改变自己的表型,通过NF-κB调控通路的影响,合成并分泌TGF-β,与IL-4协同一起调控Il9的转录。
[Abstract]:Recent reports have found that CD4 Th cell subsets have the ability to change their gene expression patterns in specific cytokine environments. We have previously found that Thl cells can produce IL-3,IL-9,IL-13 and granulocyte macrophage colony stimulating factor GM-CSF, stimulated by antigens OVA,IL-2 and IL-18 based on the unique plasticity of Thl cells. We named this class of activated Thl cells "super Thl cells" (Super Thl cells). In this paper, the primary naive CD4 T cells of mice were isolated and extracted by flow cytometry and differentiated into mature Thl cells. After IL-18 and TCR were re-stimulated, flow cytometry and enzyme-linked immunosorbent assay (Elisa) were used. The phenotypic changes of Thl were observed by RT-PCR et al. We found for the first time that the stimulation of IL-18 and T cell receptors can induce differentiated Thl cells to secrete more TGF- 尾. These TGF- 尾 play a key role in the regulation of T cells because they are involved in the secretion of IL-9 by Super Th1 cells. In addition, after the differentiated and mature Thl cells were stimulated by CD3 antibody, we found that Thl cells secrete a small amount of IL-4, at the same time. These IL-4 and TGF- 尾 work together to promote the secretion of a large number of IL-9. by Thl cells. At the same time, IL-4/STAT6 signaling pathway is also a necessary condition for the expression of IL-9. In a word, in this paper, we found and demonstrated for the first time that TGF- 尾 plays a key role in the synthesis of IL-9 by Super Thl cells. TGF- 尾 changes its phenotype under the condition of co-stimulation of IL-18 and TCR. Through the effect of NF- kappa B regulatory pathway, TGF- 尾 was synthesized and secreted, and the transcription of Il9 was regulated in conjunction with IL-4.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R392

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