2010
DOI: 10.1016/j.immuni.2010.04.010
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Toll-like Receptor 2 Signaling in CD4+ T Lymphocytes Promotes T Helper 17 Responses and Regulates the Pathogenesis of Autoimmune Disease

Abstract: SUMMARY Toll-like receptors (TLRs) have previously been shown to play critical roles in the activation of innate immunity. Here, we describe that T cell expression of TLR2 regulates T helper 17 (Th17) cell responses. Stimulation with TLR2 agonists promoted Th17 differentiation in vitro and led to more robust proliferation and Th17 cytokine production. Using the experimental autoimmune encephalomyelitis (EAE) model, we found that TLR2 regulated Th17 cell-mediated autoimmunity in vivo and that loss of TLR2 in CD… Show more

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Cited by 263 publications
(314 citation statements)
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“…Ligation of TLR-2 can exacerbate experimental autoimmune encephalomyelitis (28). Recently, this has been attributed to enhanced Th17 production (29). We found that TLR-2 ligation resulted in persistent elevation of Th17 autoimmune responses, which facilitated the development of neutrophil-mediated glomerulonephritis after administration of sheep anti- Figure 6.…”
Section: Discussionmentioning
confidence: 69%
“…Ligation of TLR-2 can exacerbate experimental autoimmune encephalomyelitis (28). Recently, this has been attributed to enhanced Th17 production (29). We found that TLR-2 ligation resulted in persistent elevation of Th17 autoimmune responses, which facilitated the development of neutrophil-mediated glomerulonephritis after administration of sheep anti- Figure 6.…”
Section: Discussionmentioning
confidence: 69%
“…EAE is attenuated in TLR2 -/-mice, suggesting that the TLR2 signaling pathway may be a drug target for the treatment or prevention of multiple sclerosis 62 . An antibody to TLR2 developed by Opsona Therapeutics has been shown to be effective in a murine model of myocardial ischemia reperfusion injury 103 , and a humanized version of the antibody (OPN-305) has recently entered phase I clinical trials.…”
Section: Tlrs and Other Pprs As Drug Targets For Autoimmunitymentioning
confidence: 99%
“…It is known that TLR stimulation of innate immune cells promotes Th1 and Th17 responses by inducing the Th1-polarizing cytokine IL-12 and the Th17-polarizing cytokines IL-6/IL-23/ IL-1 (refs 1,41). Recent studies, including ours, show that TLR2 ligands directly activate Th1 but not Th2 cells 7 and promote Th17 differentiation 8 . In contrast to TLR, the activation of RLRs suppresses Th1 and Th17 differentiation through the inhibition of IL-12 and IL-23 production, resulting in the enhanced differentiation of Th2 cells 31 .…”
Section: Discussionmentioning
confidence: 64%
“…For example, TLR2 ligands directly promote proliferation of activated T cells 3,4 , modulate the proliferation and suppressive functions of CD4 þ CD25 þ regulatory T cells 5,6 , trigger Th1 effector functions independently of TCR stimulation 7 and modulate Th17 responses 8 .…”
mentioning
confidence: 99%