Guerriero A, Langmuir P B, Spain L M, Scott E W
Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104-6140, USA.
Blood. 2000 Feb 1;95(3):879-85.
The ets-family transcription factor PU.1 is required for the proper development of both myeloid and lymphoid progenitors. We used PU. 1-deficient animals to examine the role of PU.1 during dendritic cell development. PU.1(-/-)animals produce lymphoid-derived dendritic cells (DC): low-density class II major histocompatibility complex [MHC-II(+)] CD11c(+) CD8alpha(+) DEC-205(+). But they lack myeloid-derived DC: low-density MHC-II(+) CD11c(+) CD8alpha(-) DEC-205(-). PU.1(-/-) embryos also lack progenitors capable of differentiating into myeloid DC in response to granulocyte-macrophage colony-stimulating factor plus interleukin-4. The appearance of lymphoid DC in developing PU.1(-/-)thymus was initially delayed, but this population recovered to wild type (WT) levels upon organ culture of isolated thymic lobes. PU. 1(-/-)lymphoid DC were functionally equivalent to WT DC for stimulating T-cell proliferation in mixed lymphocyte reactions. These results demonstrate that PU.1 is required for the development of myeloid DC but not lymphoid DC.
ets 家族转录因子 PU.1 是髓系和淋巴系祖细胞正常发育所必需的。我们利用 PU.1 缺陷动物来研究 PU.1 在树突状细胞发育过程中的作用。PU.1(-/-)动物可产生源自淋巴系的树突状细胞（DC）：低密度 II 类主要组织相容性复合体[MHC-II(+)] CD11c(+) CD8alpha(+) DEC-205(+)。但它们缺乏源自髓系的 DC：低密度 MHC-II(+) CD11c(+) CD8alpha(-) DEC-205(-)。PU.1(-/-)胚胎也缺乏能够在粒细胞-巨噬细胞集落刺激因子加白细胞介素-4 作用下分化为髓系 DC 的祖细胞。发育中的 PU.1(-/-)胸腺中淋巴系 DC 的出现最初有所延迟，但在分离胸腺叶的器官培养后，这一群体恢复到了野生型（WT）水平。在混合淋巴细胞反应中，PU.1(-/-)淋巴系 DC 在刺激 T 细胞增殖方面的功能与 WT DC 相当。这些结果表明，PU.1 是髓系 DC 发育所必需的，但不是淋巴系 DC 发育所必需的。
