Submitted March 1, 2006
Accepted May 30, 2006
TLR agonists promote ERK-mediated preferential IL-10 production of regulatory dendritic cells (diffDCs) leading to NK cell activation
Cheng Qian, Xiaodong Jiang, Huazhang An, Yizhi Yu, Zhenhong Guo, Shuxun Liu, Hongmei Xu, and Xuetao Cao*
Insitite of Immunology, Second Military Medical University, Shanghai, China
Institute of Immunology, Zhejiang University, Hangzhou, China
* Corresponding author; email: caoxt{at}public3.sta.net.cn.
Regulatory dendritic cells (DCs) play an important role in maintaining peripheral tolerance or immune homeostasis. Our previous study demonstrated that mature DCs could be driven by splenic stroma to proliferate and differentiate into a novel subset of regulatory DCs (diffDCs) displaying Th2-biased cytokine profile. However, the underlying mechanisms for the unique cytokine profile of diffDCs and how diffDCs regulate the innate and adaptive immunity in response to TLR agonists remain unclear. Here, we report that unlike immature DCs, diffDCs secrete more IL-10 but little IL-12p70 in response to LPS or other TLR agonists. Upregulation of ERK1/2 activation was shown to be responsible for IL-10 preferential production, and suppression of p38 activation was for impaired IL-12p70 production in diffDCs. Interestingly, LPS treatment could not reverse the inhibitory effect of diffDCs on the proliferation of antigen-specific CD4+ T cells. However, diffDCs could activate NK cells through diffDCs-derived IL-10, and even more markedly after TLR agonists stimulation. These diffDCs-activated NK cells could in turn kill surrounding diffDCs. Our results illuminate signal pathways for the unique cytokine profile of diffDCs, and diffDCs can exert their regulatory function even after inflammatory stimuli, thus reflecting one way for strict regulation of immune response.
