Blockade of TLR9 agonist-induced type I interferons promotes inflammatory cytokine IFN-γ and IL-17 secretion by activated human PBMC

Meyers, John A.; Mangini, Alyson J.; Nagai, Toshiaki; Roff, Calvin F.; Sehy, David; Seventer, Gijs A. van; Seventer, Jean Maguire van

doi:10.1016/j.cyto.2006.09.001

Cited by 33 publications

(27 citation statements)

References 60 publications

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“…Our findings support not only our in vitro findings but also demonstrate that an enhanced IL-17 expression might contribute to disease pathology observed in IBD, especially in UC where neutrophilic infiltration and crypt abscesses play a major role. Our results are also in accordance with data presented by Meyers et al (2006), who demonstrated that blockade of TLR9 agonist-induced type I IFNs enhanced not only IFN-gamma but also IL-17 production by PBMC. IFNa-induced suppression of IL-17 could, therefore, contribute to its anti-inflammatory and disease-modifying properties.…”

Section: Article In Presssupporting

confidence: 96%

Interferon-alpha controls IL-17 expression in vitro and in vivo

Moschen¹,

Geiger²,

Krehan³

et al. 2008

Immunobiology

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Section: Article In Presssupporting

confidence: 96%

Interferon-alpha controls IL-17 expression in vitro and in vivo

Moschen¹,

Geiger²,

Krehan³

et al. 2008

Immunobiology

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“…Despite the anti-proliferative effect, a general anti-inflammatory function of both type I IFNs and TLR9 is observed in an experimental colitis model and exacerbation of SLE-like symptoms in the respective genetic-deficient mice (Lau et al, 2005;Pisitkun et al, 2006). In support of this mouse data is a newly developed in vitro model of human PBMC stimulation, where pretreatment with either type I interferon or TLR9 ligands inhibited the secretion of proinflammatory cytokines (Meyers et al, 2006). The antagonism of pro-or anti-inflammatory action of the nucleic acid-recognizing TLRs in SLE-like murine disease also has a biochemical signaling aspect.…”

Section: How Does Tlr9 Act As An Anti-inflammatory Receptor In Vivo?supporting

confidence: 49%

Toll-like receptor 9 in murine lupus: More friend than foe!

Musette

Peng

2008

Immunobiology

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“…Meyers et al . showed that type I interferon (IFN) can inhibit IL-17 production in human peripheral blood mononuclear cells (PBMCs), suggesting a repressive effect of type I IFN on Th17 cells [39]. Studies investigating the relationship between IL-17 and type I IFN in human SLE would be of interest.…”

Section: Discussionmentioning

confidence: 99%

Clinical associations of serum interleukin-17 in systemic lupus erythematosus

et al. 2013

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IntroductionSerum interleukin (IL)-17 concentrations have been reported to be increased in systemic lupus erythematosus (SLE), but associations with clinical characteristics are not well understood. We characterized clinical associations of serum IL-17 in SLE.MethodsWe quantified IL-17 in serum samples from 98 SLE patients studied cross-sectionally, and in 246 samples from 75 of these patients followed longitudinally over two years. Disease activity was recorded using the SLE Disease Activity Index (SLEDAI)-2k. Serum IL-6, migration inhibitory factor (MIF), and B cell activating factor of the tumour necrosis factor family (BAFF) were also measured in these samples.ResultsSerum IL-17 levels were significantly higher in SLE patients compared to healthy donors (P <0.0001). No correlation was observed between serum IL-17 and SLEDAI-2k, at baseline or during longitudinal follow-up. However, we observed that SLEDAI-2k was positively correlated with IL-17/IL-6 ratio. Serum IL-17 was significantly increased in SLE patients with central nervous system (CNS) disease (P = 0.0298). A strong correlation was observed between serum IL-17 and IL-6 (r = 0.62, P <0.0001), and this relationship was observed regardless of disease activity and persisted when integrating cytokine levels over the period observed (r = 0.66, P <0.0001). A strong correlation of serum IL-17 was also observed with serum BAFF (r = 0.64, P <0.0001), and MIF (r = 0.36, P = 0.0016).ConclusionsSerum IL-17 concentration correlates poorly with SLE disease activity but is significantly elevated in patients with CNS disease. IL-17/IL-6 ratio may be more useful than IL-17 or IL-6 alone to characterize Th17-driven disease, such as SLE. The association of other cytokines with serum IL-17 suggests that IL-17 may drive activation of diverse immune pathways in SLE.

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Blockade of TLR9 agonist-induced type I interferons promotes inflammatory cytokine IFN-γ and IL-17 secretion by activated human PBMC

Cited by 33 publications

References 60 publications

Interferon-alpha controls IL-17 expression in vitro and in vivo

Interferon-alpha controls IL-17 expression in vitro and in vivo

Toll-like receptor 9 in murine lupus: More friend than foe!

Clinical associations of serum interleukin-17 in systemic lupus erythematosus

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