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Cited by 518

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Endogenous ligands of TLR2 and TLR4: agonists or assistants?

Erridge, Clett·2010·Journal of Leukocyte Biology

Abstract

Review summarizes the evidence supporting the existence of endogenous ligands of TLR2 and TLR4 and proposes that many may be better described as PAMP-sensitizing molecules. The mammalian TLRs serve as key sensors of PAMPs, such as bacterial LPS, lipopeptides, and flagellins, which are present in microbial cells but not host cells. TLRs have therefore been considered to play a central role in the discrimination between “self” and “non-self”. However, since the discovery of their microbial ligands, many studies have provided evidence that host-derived molecules may also stimulate TLR2- or TLR4-dependent signaling. To date, more than 20 of these endogenous TLR ligands have been proposed, which have tended to fall into the categories of released intracellular proteins, ECM components, oxidatively modified lipids, and other soluble mediators. This review aims to summarize the evidence supporting the intrinsic TLR-stimulating capacity of each of these proposed endogenous ligands with a particular emphasis on the measures taken to exclude contaminating LPS and lipopeptides from experimental systems. The emerging evidence that many of these molecules may be more accurately described as PAMP-binding molecules (PBMs) or PAMP-sensitizing molecules (PSMs), rather than genuine ligands of TLR2 or TLR4, is also summarized. The relevance of this possibility to the pathogenesis of chronic inflammatory diseases, tumor surveillance, and autoimmunity is discussed.

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Metadata

Authors
Erridge, C.
Venue
Journal of Leukocyte Biology
Published
2010-02-23
Volume
87
Issue
6
Pages
989-999
ISSN
  • 0741-5400 (ISSN-L)
  • 1938-3673
OpenAlex
W1993792235
Cited by
518
References
21
FWCI
18.38
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Endogenous ligands of TLR2 and TLR4: agonists or assistants? https://app.cochat.ai/papers/10.1189/jlb.1209775
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Erridge, C. (2010). Endogenous ligands of TLR2 and TLR4: agonists or assistants? Journal of Leukocyte Biology. https://doi.org/10.1189/jlb.1209775

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