Submitted January 20, 2006
Accepted March 21, 2006
Endothelial stroma programs hematopoietic stem cells to
differentiate into regulatory dendritic cells through IL-
10
Hua Tang, Zhenhong Guo, Minghui Zhang, Jianli Wang, Guoyou Chen, and Xuetao Cao*
Institute of Immunology, Zhejiang University, Hangzhou 310031, P.R.China
Institute of Immunology, Second Military Medical University, Shanghai 200433, P.R.China
* Corresponding author; email: caoxt{at}public3.sta.net.cn.
Regulatory dendritic cells (DCs) have been reported
recently, but their origin is poorly understood. Our
previous study demonstrated that splenic stroma can
drive mDCs to proliferate and differentiate into
regulatory DCs and their natural counterpart with
similar regulatory function in normal spleen is
identified. Considering that spleen microenvironment
supports hematopoiesis and hematopoietic stem cells
(HSCs) are found in spleen of adult mice, we wonder
whether splenic microenvironment could differentiate
HSCs into regulatory DCs. In this report, we demonstrate
that endothelial splenic stroma induces HSCs to
differentiate into a distinct regulatory DCs subset
which high express CD11b but low express Ia. CD11bhiIalo
DCs secreting high level of TGF-[[beta]] , IL-10, NO can
suppress T cell proliferation both in vitro and in vivo.
Furthermore, CD11bhiIalo DCs have the ability to
potently suppress allo-DTH in vivo, indicating their
preventive or therapeutic perspectives for some
immunological disorders. The inhibitory function of
CD11bhiIalo DCs is mediated through NO but not through
induction of Treg or T cell anergy. IL-10, secreted by
endothelial splenic stroma, plays a critical role in the
differentiation of the regulatory CD11bhiIalo DCs from
HSCs. These results suggest that splenic
microenvironment may physiologically induce regulatory
DC differentiation in situ.
