FoxP3+ regulatory T cells restrain splenic extramedullary myelopoiesis via suppression of hemopoietic cytokine-producing T cells.
FoxP3+ regulatory T cells restrain splenic extramedullary myelopoiesis via suppression of hemopoietic cytokine-producing T cells.
复制标题
DOI：
10.4049/jimmunol.0901268
复制
发表时间：
2009-11-15
期刊：
影响因子：
--
通讯作者：
Kim CH
中科院分区：
文献类型：
--
作者：
Lee JH;Wang C;Kim CH
髓外髓系造血发生于脾等外周器官，可产生多种功能不同的髓系细胞，以应对炎症和感染。它在免疫反应和慢性炎症过程中增加，是调节炎症性疾病和免疫的重要因素。在FoxP3基因缺陷的小鼠中发现髓系细胞增加，但其机制尚不清楚。我们研究了FoxP3+调节性T细胞调节髓外骨髓生成的机制。我们发现，在免疫应答过程中，FoxP3+调节性T细胞的抗体或遗传耗竭大大增加了脾中髓系祖细胞的数量。一直以来，脾的骨髓生成被自然或诱导的FoxP3+调节性T细胞数量的增加有效地抑制。我们证明了脾中产生造髓细胞因子(GM-CSF和IL-3)的CD4+T细胞能正向调节骨髓生成，这些效应细胞是在抗原刺激下从幼稚的CD4+T细胞诱导而来的。Foxp3+调节性T细胞能有效抑制幼稚T细胞向髓系细胞因子T细胞的分化。这种抑制依赖于细胞接触，但不依赖于转化生长因子-β。与脾造血不同，骨髓造血不受FoxP3+调节性T细胞的显著影响。结论：FoxP3+T细胞可通过抑制原始T细胞分化为产生造髓细胞因子的CD4+T细胞，对脾髓外髓外髓系细胞的生成起负性调节作用。我们的结果为髓外骨髓生成的调控提供了新的见解。
Extramedullary myelopoiesis occurs in peripheral organs such as spleen and produces many types of myeloid cells with diverse functions in response to inflammation and infection. It is increased during immune responses and chronic inflammation and is a significant factor in regulating inflammatory diseases and immunity. Increased myeloid cells are found in FoxP3-deficient mice but the mechanism has been unclear. We investigated the mechanism by which FoxP3+ regulatory T cells regulate the extramedullary myelopoiesis. We found that antibody or genetic depletion of FoxP3+ regulatory T cells greatly increased the number of the myeloid progenitors in spleen during immune responses. Consistently, the splenic myelopoiesis was effectively suppressed by increased numbers of natural or induced FoxP3+ regulatory T cells. We demonstrated that myelopoiesis is positively regulated by splenic CD4+ T cells that produce myelopoietic cytokines (GM-CSF and IL-3), and these effector CD4+ T cells are induced from naïve CD4+ T cells in response to antigenic stimulation. FoxP3+ regulatory T cells were able to effectively suppress the differentiation of naïve T cells into myelopoietic cytokine-producing T cells. This suppression was found to be dependent on cell-contact but independent of TGF-β. Unlike splenic myelopoiesis, marrow myelopoiesis is not significantly affected by FoxP3+ regulatory T cells. We conclude that FoxP3+ T cells can negatively regulate splenic extramedullary myelopoiesis by suppressing the naïve T cell differentiation into myelopoietic cytokine-producing CD4+ T cells. Our results provide new insights into regulation of extramedullary myelopoiesis.
登录
查看更多内容
影响因子：
4.4
作者：
Biondo, M;Nasa, Z;Alderuccio, F
通讯作者：
Alderuccio, F
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1073/pnas.87.7.2433
发表时间：
1990-04-01
影响因子：
11.1
作者：
LYON, MF;PETERS, J;WRIGHT, E
通讯作者：
WRIGHT, E
影响因子：
2.6
作者：
Arellano-Rodrigo, E;Esteve, J;Cervantes, F
通讯作者：
Cervantes, F
影响因子：
14.2
作者：
Lin, W;Truong, N;Chatila, TA
通讯作者：
Chatila, TA