Toll-like Receptor 9–Dependent and –Independent Dendritic Cell Activation by Chromatin–Immunoglobulin G Complexes

Journal of Experimental Medicine - Tập 199 Số 12 - Trang 1631-1640 - 2004
Melissa B. Uccellini1, Courtney Broughton2, Fabienne Mackay3, Shizuo Akira4, Ann Marshak‐Rothstein5, Ian R. Rifkin2
1Renal Section, Department of Medicine, Boston University School of Medicine, EBRC 5th Floor, 650 Albany Street, Boston, MA 02118, USA.
21Renal Section, Department of Medicine
33Department of Arthritis and Inflammation, Garvan Institute of Medical Research, New South Wales 2010, Australia
4Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
5Department of Microbiology, Boston University School of Medicine, Boston, MA 02118

Tóm tắt

Dendritic cell (DC) activation by nucleic acid–containing immunoglobulin (Ig)G complexes has been implicated in systemic lupus erythematosus (SLE) pathogenesis. However, the mechanisms responsible for activation and subsequent disease induction are not completely understood. Here we show that murine DCs are much more effectively activated by immune complexes that contain IgG bound to chromatin than by immune complexes that contain foreign protein. Activation by these chromatin immune complexes occurs by two distinct pathways. One pathway involves dual engagement of the Fc receptor FcγRIII and Toll-like receptor (TLR)9, whereas the other is TLR9 independent. Furthermore, there is a characteristic cytokine profile elicited by the chromatin immune complexes that distinguishes this response from that of conventional TLR ligands, notably the induction of BAFF and the lack of induction of interleukin 12. The data establish a critical role for self-antigen in DC activation and explain how the innate immune system might drive the adaptive immune response in SLE.

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Thông tin xuất bản

Journal of Experimental Medicine

Tập 199 Số 12

1631-1640

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