The IL-23/Th17 axis: therapeutic targets for autoimmune inflammation

Kikly, Kristine; Liu, Ling; Na, Songqing; Sedgwick, Jonathon D.

doi:10.1016/j.coi.2006.09.008

Cited by 270 publications

(216 citation statements)

References 55 publications

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“…Mice lacking IL-23p19 but not IL-12p35 were resistant to autoimmune inflammatory diseases, including experimental autoimmune encephalomyelitis and inflammatory bowel disease (28). Furthermore, emerging data support that IL-23 is closely linked to autoimmune inflammatory diseases in humans.…”

Section: Discussionmentioning

confidence: 95%

Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A

Chang

Voorhees

Liu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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IL-12 and IL-23 are produced by activated antigen-presenting cells but the two induce distinct immune responses by promoting Th1 and Th17 cell differentiation, respectively. IL-23 is a heterodimeric cytokine consisting of two subunits: p40 that is shared with IL-12 and p19 unique to IL-23. In this study, we showed that the production of IL-23 but not IL-12 was negatively regulated by protein phosphatase 2A (PP2A) in dendritic cells (DC). PP2A inhibits IL-23 production by suppressing the expression of the IL-23p19 gene. Treating DC with okadaic acid that inhibits the PP2A activity or knocking down the catalytic subunit of PP2A with siRNA enhanced IL-23 but not IL-12 production. Unlike PP2A, MAP kinase phosphatase-1 or CYLD did not show an effect on IL-23 production supporting the specificity of PP2A. PP2A-mediated inhibition requires a newly made protein that is likely responsible for bringing PP2A and IKKβ together upon LPS stimulation, which then results in the termination of IKK phosphorylation. Thus, our results uncovered an important role of the protein phosphatase in the regulation of IL-23 production and identified PP2A as a previously uncharacterized inhibitor of IL-23p19 expression in DC.cytokine | NF-κB | TLR

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Section: Discussionmentioning

confidence: 95%

Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A

Chang

Voorhees

Liu

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…20 IL-23 is emerging as a new and powerful regulator of autoimmune inflammation by supporting the expansion of Th17 cells. 37 Synergistic effects of IFN-␣ and lipopolysaccharide are probably not restricted to these effector cytokines but likely involve a whole battery of cytokines via the NF-B pathway. Moreover, TLR4 signaling promotes foam cell formation by increasing cholesteryl ester and triglyceride levels in macrophages.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Proinflammatory Effects of the Antiviral Cytokine Interferon-α and Toll-Like Receptor 4 Ligands in the Atherosclerotic Plaque

et al. 2007

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“…Their differentiation is inhibited by IFN-gamma, IL-4 and IL-2 [102]. Genetic analysis of these Th17 cells identified a unique expression pattern of pro-inflammatory cytokines and revealed a unique role in different mouse models of autoimmune inflammation [103]. Given that the levels of IL-23 p19 and IL-17 are elevated in human diseases including multiple sclerosis, psoriasis and Crohn's disease, it is possible that these cytokines mediate human diseases [104][105][106].…”

Section: Il-12 and Its Familymentioning

confidence: 99%

Dendritic cells and cytokines in human inflammatory and autoimmune diseases

Blanco

Palucka

Pascual

et al. 2008

Cytokine & Growth Factor Reviews

440

359

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Dendritic cells (DCs) produce cytokines and are susceptible to cytokine-mediated activation. Thus, interaction of resting immature DCs with TLR ligands, for example nucleic acids, or with microbes leads to a cascade of pro-inflammatory cytokines and skewing of T cell responses. Conversely, several cytokines are able to trigger DC activation (maturation) via autocrine, for example TNF and plasmacytoid DCs, and paracrine, for example type I IFN and myeloid DCs, pathways. By controlling DC activation, cytokines regulate immune homeostasis and the balance between tolerance and immunity. The increased production and/or bioavailability of cytokines and associated alterations in DC homeostasis have been implicated in various human inflammatory and autoimmune diseases. Targeting these cytokines with biological agents as already is the case with TNF and IL-1 represents a success of immunology and the coming years will expand the range of cytokines as therapeutic targets in autoinflammatory and autoimmune pathology.

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The IL-23/Th17 axis: therapeutic targets for autoimmune inflammation

Cited by 270 publications

References 55 publications

Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A

Interleukin-23 production in dendritic cells is negatively regulated by protein phosphatase 2A

Synergistic Proinflammatory Effects of the Antiviral Cytokine Interferon-α and Toll-Like Receptor 4 Ligands in the Atherosclerotic Plaque

Dendritic cells and cytokines in human inflammatory and autoimmune diseases

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