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Cited by 373

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Regulation of Toll-like receptor–mediated inflammatory response by complement in vivo

Open access
Zhang, Xinhua, Kimura, Yuko, Fang, Chongyun, Zhou, Lin, Sfyroera, Georgia, Lambris, John D., Wetsel, Rick A., Miwa, Takashi, Song, Wen-Chao·2007·Blood

Abstract

Toll-like receptors (TLRs) and complement are 2 components of innate immunity that are critical for first-line host defense and elicitation of adaptive immune responses. Many pathogen-associated molecular patterns activate both TLR and complement, but whether and how these 2 systems, when coactivated in vivo, interact with each other has not been well studied. We demonstrate here a widespread regulation of TLR signaling by complement in vivo. The TLR ligands lipopolysacharride (TLR4), zymosan (TLR2/6), and CpG oligonucleotide (TLR9) caused, in a complement-dependent manner, strikingly elevated plasma interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β, and/or decreased plasma IL-12 levels in mice deficient in the membrane complement inhibitor decay-accelerating factor (DAF). A similar outcome was observed in wild-type mice cotreated with the TLR ligands and cobra venom factor, a potent complement activator. The regulatory effect of complement on TLR-induced cytokine production in vivo was mediated by the anaphylatoxin receptors C5aR and C3aR. Additionally, changes in lipopolysaccharide (LPS)–induced cytokine production in DAF-deficient mice correlated with increased mitogen-activated protein kinase and nuclear factor-κB activation in the spleen. These results reveal a strong interaction between complement and TLR signaling in vivo and suggest a novel mechanism by which complement promotes inflammation and modulates adaptive immunity.

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Crossref · 10.1182/blood-2006-12-063636

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Metadata

Authors
Zhang, X., Kimura, Y., Fang, C., Zhou, L., Sfyroera, G., Lambris, J. D., Wetsel, R. A., Miwa, T., & Song, W.-C.
Venue
Blood
Published
2007-07-01
Volume
110
Issue
1
Pages
228-236
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2107489987
Cited by
373
References
47
FWCI
8.78
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Regulation of Toll-like receptor–mediated inflammatory response by complement in vivo. https://app.cochat.ai/papers/10.1182/blood-2006-12-063636
The paper
Zhang, X., Kimura, Y., Fang, C., Zhou, L., Sfyroera, G., Lambris, J. D., Wetsel, R. A., Miwa, T., & Song, W.-C. (2007). Regulation of Toll-like receptor–mediated inflammatory response by complement in vivo. Blood. https://doi.org/10.1182/blood-2006-12-063636

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