Toll-like Receptor 9–Dependent and –Independent Dendritic Cell Activation by Chromatin–Immunoglobulin G Complexes
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- Melissa W. Boulé
- 1Renal Section, Department of Medicine
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- Courtney Broughton
- 1Renal Section, Department of Medicine
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- Fabienne Mackay
- 3Department of Arthritis and Inflammation, Garvan Institute of Medical Research, New South Wales 2010, Australia
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- Shizuo Akira
- 4Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
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- Ann Marshak-Rothstein
- 2Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
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- Ian R. Rifkin
- 1Renal Section, Department of Medicine
抄録
<jats:p>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.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 199 (12), 1631-1640, 2004-06-14
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1360574096576600832
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- NII論文ID
- 30017417586
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- ISSN
- 15409538
- 00221007
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- データソース種別
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