Hedgehog signaling regulates differentiation from double-negative to double-positive thymocyte

被引：143
|
作者：
Outram, SV
Varas, A
Pepicelli, CV
Crompton, T
机构：
[1] Univ London Imperial Coll Sci Technol & Med, Dept Biol, London SW7 2AZ, England
[2] Ontogeny Inc, Skin Grp, Cambridge, MA 02138 USA
来源：
IMMUNITY | 2000年 / 13卷 / 02期
基金：
英国惠康基金;
关键词：
D O I：
10.1016/S1074-7613(00)00019-4
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
The hedgehog (Hh) signaling pathway is involved in the development of many tissues. Here we show that sonic hedgehog (Shh) is involved in thymocyte development. Our data suggest that termination of Hh signaling is necessary for differentiation from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) double-positive (DP) thymocyte. Shh is produced by the thymic stroma, and Patched and Smoothened (Smo), the transmembrane receptors for Shh, are expressed in DN thymocytes. A neutralizing monoclonal antibody against Shh increases differentiation of DN to DP thymocytes, and Shh protein arrests thymocyte differentiation at the CD25(+) DN stage, after T cell receptor beta (TCR beta) gene rearrangement. We show that one consequence of pre-TCR signaling is downregulation of Smo, allowing DN thymocytes to proliferate and differentiate.
引用
收藏
页码：187 / 197
页数：11
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