Notch signaling regulates the development of a novel type of Thy1-expressing dendritic cell in the thymus
Notch signaling regulates the development of a novel type of Thy1-expressing dendritic cell in the thymus
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DOI：
10.1002/eji.201041159
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发表时间：
2011-05-01
影响因子：
5.4
通讯作者：
Yasutomo, Koji
中科院分区：
文献类型：
--
作者：
Ishifune, Chieko;Maekawa, Yoichi;Yasutomo, Koji
树突状细胞（Dendritic cells，DC）是T细胞活化所需的特异性抗原呈递细胞（antigen presenting cells，APC），根据表型和功能特征可分为几种亚型。然而，目前还不清楚是否有不同的转录因子控制每个DC亚群的发展。在这份报告中，我们证明了Notch信号控制一种新的表达Thy 1的DC亚型（Thy 1（+）DC）的发展。Notch配体Delta-like 1过度刺激骨髓细胞可促进Thy 1（+）DC的发育。Thy 1（+）DC的特征为CD 11 c（+）MHC II类（+）NK1.1（-）B220（-）CD 8 α（+），存在于胸腺中，但不存在于脾和淋巴结中。胸腺Thy 1（+）DC能够捕获外源蛋白并删除CD 4（+）CD 8（+）T细胞。移植实验表明，CD 44（+）CD 25（-）和CD 44（+）CD 25（+）胸腺细胞可分化为Thy 1（+）DC。免疫球蛋白κ J区（RBP-J）缺陷的信号结合蛋白在谱系阴性的骨髓细胞（而不是CD 11 c（+）细胞）中破坏胸腺中Thy 1（+）DC的发育。我们的数据表明，Notch信号控制一种新型的Thy 1表达DC的胸腺，可能控制负选择的发展，并表明可能有高度调节，DC发展的差异转录控制。此外，我们的研究结果表明，Notch信号不仅通过内在诱导T细胞谱系特异性基因程序来调节T细胞发育，而且还通过Thy 1（+）DCs调节负选择。
Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) required for T-cell activation and are classified into several subtypes by phenotypic and functional characteristics. However, it remains unclear if distinct transcription factors control the development of each DC subpopulation. In this report, we demonstrate that Notch signaling controls the development of a novel DC subtype that expresses Thy1 (Thy1(+)DCs). Overstimulation of bone marrow cells with the Notch ligand Delta-like 1 promoted the development of Thy1(+)DCs. Thy1(+)DCs are characterized as CD11c(+)MHC class II(+)NK1.1(-)B220(-)CD8 alpha(+), and are present in the thymus but not in the spleen and lymph nodes. Thymic Thy1(+)DCs are able to capture exogenous proteins and delete CD4(+)CD8(+) T cells. Transplantation experiments demonstrated that CD44(+)CD25(-) and CD44(+)CD25(+) thymocytes can differentiate into Thy1(+) DCs. Recombination signal binding protein for immunoglobulin kappa J region (RBP-J) deficiency in lineage-negative bone marrow cells, but not CD11c(+) cells, disrupted Thy1(+)DC development in the thymus. Our data indicate that Notch signaling controls the development of a novel type of Thy1-expressing DC in the thymus that possibly controls negative selection, and indicates that there may be highly regulated, differential transcriptional control of DC development. Furthermore, our findings suggest that Notch signaling regulates T-cell development not only by intrinsically inducing T-cell lineage-specific gene programs, but also by regulating negative selection through Thy1(+)DCs.