Psoriasis induced by topical imiquimod

Wu, Jason; Siller, Greg; Strutton, Geoff

doi:10.1111/j.1440-0960.2004.00030.x

Cited by 131 publications

(91 citation statements)

References 20 publications

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“…IMQ can exacerbate psoriasis in patients with a well-controlled psoriasis during topical treatment of actinic keratoses and superficial basal cell carcinomas (4 -7). IMQinduced exacerbation of psoriasis occurs at both the treated area and, interestingly, also at distant skin sites that were previously unaffected (5)(6)(7). Furthermore suggestive for systemic effects of topical IMQ application are our own clinical observations that patients with IMQ-induced psoriasis at distant body sites exhibit flulike symptoms (unpublished data).…”

mentioning

confidence: 83%

Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis

Fits

Mourits

Voerman³

et al. 2009

The Journal of Immunology

1,758

104

1,698

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Topical application of imiquimod (IMQ), a TLR7/8 ligand and potent immune activator, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. Recently, a crucial role was proposed for the IL-23/IL-17 axis in psoriasis. We hypothesized that IMQ-induced dermatitis in mice can serve as a model for the analysis of pathogenic mechanisms in psoriasis-like dermatitis and assessed its IL-23/IL-17 axis dependency. Daily application of IMQ on mouse back skin induced inflamed scaly skin lesions resembling plaque type psoriasis. These lesions showed increased epidermal proliferation, abnormal differentiation, epidermal accumulation of neutrophils in microabcesses, neoangiogenesis, and infiltrates consisting of CD4+ T cells, CD11c+ dendritic cells, and plasmacytoid dendritic cells. IMQ induced epidermal expression of IL-23, IL-17A, and IL-17F, as well as an increase in splenic Th17 cells. IMQ-induced dermatitis was partially dependent on the presence of T cells, whereas disease development was almost completely blocked in mice deficient for IL-23 or the IL-17 receptor, demonstrating a pivotal role of the IL-23/IL-17 axis. In conclusion, the sole application of the innate TLR7/8 ligand IMQ rapidly induces a dermatitis closely resembling human psoriasis, critically dependent on the IL-23/IL-17 axis. This rapid and convenient model allows further elucidation of pathogenic mechanisms and evaluation of new therapies in psoriasis.

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mentioning

confidence: 83%

Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis

Fits

Mourits

Voerman³

et al. 2009

The Journal of Immunology

1,758

104

1,698

View full text Add to dashboard Cite

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“…This model, which is IL-23 dependent, involves daily topical application of the TLR7 agonist imiquimod formulated in a commercially available cream, Aldara (28). Aldara has been used for some time in the treatment of a variety of dermal malignancies such as actinic keratoses and superficial basal cell carcinomas (29,30); however, a side effect of such treatment is the exacerbation of psoriatic lesions in some patients, even those with well controlled psoriasis (31,32). On the basis of this observation, use of Aldara in murine studies as an inducer of psoriasiform inflammation has come to be accepted as a clinically faithful model of psoriasis, particularly as the pathological manifestations induced bear striking similarities to human psoriasis but also because it is responsive to a range of the current frontline psoriasis therapies (9,10,28).…”

Section: Resultsmentioning

confidence: 99%

Toll IL-1R8/Single Ig IL-1–Related Receptor Regulates Psoriasiform Inflammation through Direct Inhibition of Innate IL-17A Expression by γδ T Cells

Russell

Stefańska

Kubica

et al. 2013

The Journal of Immunology

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Expression of the orphan receptor Toll IL-1R8/single Ig IL-1–related receptor has been reported to be reduced in the peripheral blood of psoriatic arthritis patients. However whether TIR8/SIGIRR activity plays a specific role in regulating psoriatic inflammation is unknown. We report that Tir8/Sigirr-deficient mice develop more severe psoriatic inflammation in both the chemical (Aldara)- and cytokine (rIL-23)-induced models of psoriasis. Increased disease severity was associated with enhanced infiltration of Vγ4+ γδ T cells that express significantly elevated levels of IL-17A. Critically, we also demonstrate that TIR8/SIGIRR activity directly suppressed innate IL-17A expression by γδ T cells in vitro and in vivo. Importantly, treatment of Tir8/Sigirr−/− mice with an IL-17A neutralization Ab reversed the enhanced disease severity observed in these mice. This study identifies TIR8/SIGIRR as a novel intrinsic negative regulator of innate IL-17A expression and characterizes a novel mechanism involved in the regulation of psoriatic inflammation.

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“…In contrast, levels of TLR5 are lower in psoriatic than in nonlesional epidermis. Most interestingly, several cases are described in literature where topical applications of the TLR7 agonist imiquimod lead to aggravation of psoriatic plaques (122)(123)(124)(125).…”

Section: Tlrs In Psoriasismentioning

confidence: 99%

TLRs and chronic inflammation

Ospelt

Gay

2010

The International Journal of Biochemistry & Cell Biology

162

127

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After the discovery of Toll-like receptors (TLRs), innate immune mechanisms came back in the focus of scientific research. With more and more mechanisms of TLR biology known, it has become clear that these and also other innate immune receptors are not only of crucial importance in the immune response to invading pathogens, but also play a role in the homeostasis of commensal flora and in the response to stress and danger signals. In this respect, increasing evidence is found that inappropriate quantity or quality of TLR ligands or aberrant response to TLR activation plays a role in a variety of chronic inflammatory diseases. In this review, an overview of the currently known TLRs and their signaling pathways is given and reports about their expression and activation in chronic inflammatory diseases are recapitulated. TLRs and chronic inflammation Abstract:After the discovery of Toll-like receptors (TLRs), innate immune mechanisms came back in the focus of scientific research. With more and more mechanisms of TLR biology known, it has become clear that these and also other innate immune receptors are not only of crucial importance in the immune response to invading pathogens, but also play a role in the homeostasis of commensal flora and in the response to stress and danger signals. In this respect, increasing evidence is found that inappropriate quantity or quality of TLR ligands or aberrant response to TLR activation plays a role in a variety of chronic inflammatory diseases.In this review, an overview of the currently known TLRs and their signaling pathways isgiven and reports about their expression and activation in chronic inflammatory diseases are recapitulated.2

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Psoriasis induced by topical imiquimod

Cited by 131 publications

References 20 publications

Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis

Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice Is Mediated via the IL-23/IL-17 Axis

Toll IL-1R8/Single Ig IL-1–Related Receptor Regulates Psoriasiform Inflammation through Direct Inhibition of Innate IL-17A Expression by γδ T Cells

TLRs and chronic inflammation

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