Increased TLR responses in dendritic cells lacking the ITAM-containing adapters DAP12 and FcRγ

被引:55
作者
Chu, Ching-Liang [2 ]
Yu, Yen-Ling [2 ]
Shen, Kuan-Yin [2 ]
Lowell, Clifford A.
Lanier, Lewis L. [3 ,4 ]
Hamerman, Jessica A. [1 ]
机构
[1] Benaroya Res Inst Virginia Mason, Program Immunol, Seattle, WA 98101 USA
[2] Natl Hlth Res Inst, Immunol Res Ctr, Taipei, Taiwan
[3] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Inst Canc Res, San Francisco, CA 94143 USA
关键词
antigen presentation; dendritic cell; TLR;
D O I
10.1002/eji.200737600
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 inhibitory effect of DAP12 on macrophages has been revealed by examining myeloid cells from DAP12-deficient mice. In this report, we demonstrate that both DAP12 and the FccRI gamma-chain (FcR gamma) are required for negative regulation of TLR responses in bone marrow-derived dendritic cells (DC). Loss of both DAP12 and FcR gamma enhanced the proinflammatory cytokine production and maturation of DC after TLR stimulation, resulting in a greater percentage of DC that produced IL-12 p40, TNF, and IL-6, and expressed high levels of MHC class II, CD80, and CD86. Whereas DC lacking only DAP12 showed some increased TLR responses, those lacking only FcR gamma had a greater enhancement of maturation and cytokine production, though to a lesser extent than DC lacking both DAP12 and FcR gamma. Additionally, antigen-specific T cell proliferation was enhanced by DAP12(-/-)FcR gamma(-/-) DC relative to wild-type DC after maturation. Similar to DAP12(-/-)FcR gamma(-/-) DC, Syk-deficient DC also had increased inflammatory cytokine production, maturation, and antigen presentation. These results confirm the inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM) signaling in myeloid cells and show that DC and macrophages differ in their dependence on the ITAM-containing adapters DAP12 and FcR gamma for negative regulation of TLR signaling.
引用
收藏
页码:166 / 173
页数:8
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