Sensory nerves mediate spontaneous behaviors in addition to inflammation in a murine model of psoriasis

Kodji, Xenia; Arkless, Kate; Kee, Zizheng; Cleary, Simon J.; Aubdool, Aisah A.; Evans, Elizabeth; Caton, Paul; Pitchford, Simon; Brain, Susan D.

doi:10.1096/fj.201800395rr

Cited by 36 publications

(40 citation statements)

References 76 publications

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“…4F). Recent studies reported that TRPV1 + Nav1.8 + nociceptors regulated the IL‐23/IL‐17 pathway and controlled cutaneous immune responses, and that sensory nerves mediate inflammation in psoriasis mice models 35‐37 . The results of the present study showed that the expression level of Trpv1 mRNA in ES/IMQ‐treated mice increased obviously on day 7 while the expression level of Nav1.8 increased on day 14 compared with IMQ‐treated mice (Fig.…”

Section: Discussionsupporting

confidence: 58%

Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasis and IL-1β/IL-23p40 production

Wang

Zhang

et al. 2020

Journal of Leukocyte Biology

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Psoriasis is a common, chronic multifactorial inflammatory skin disease with both genetic and environmental components. A number of studies have suggested that psoriasis episodes are often preceded by stressful life events. Nevertheless, the underline mechanisms of stress in psoriasis remain unexplored. To address this question, we established an emotional stress mouse model induced by empty bottle stimulation, and applied imiquimod (IMQ), a ligand of TLR7/8 and effective potent immune activator, on the dorsal skin to induce psoriasis‐like lesions. We found that empty bottles induced emotional stress exaggerated and prolonged psoriasiform dermatitis, which appeared as more prominent epidermal hyperplasia in the emotional stress mice compared with the control mice. Higher mRNA expression of Il‐1β, Il‐17a, and Il‐22, as well as higher secretion of IL‐1β, IL‐12p40, IL‐17, and IL‐22 were observed in the skin lesion of emotional stress mice. The emotional stress condition and IMQ treatment synergistically led to higher expression levels of neurotransmitters and their receptors in the skin, especially substance P (SP), we also found that SP could stimulate DCs to secrete more IL‐23p40 in vitro. In addition, NK‐1R antagonist partially abrogated enhanced epidermal thickness and the level of neurotransmitters in emotional stress mice. Taken together, these results indicate that stress exacerbates and prolongs psoriasiform dermatitis in mice by up‐regulating IL‐1β and IL‐23p40, which were related to local DCs stimulated by abnormal SP.

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Section: Discussionsupporting

confidence: 58%

Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasis and IL-1β/IL-23p40 production

Wang

Zhang

et al. 2020

Journal of Leukocyte Biology

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“…In psoriasis ROS and RNS play a critical role in its pathology inducing oxidative and nitrosative stress activating TRPA1 channels on sensory nerves innervating the skin, causing the release of SP and CGRP. In a preclinical model of psoriasis, TRPA1 antagonists significantly inhibited itching, however it Is important to note that long term treatment with a TRPA1 antagonist or TRPA1 deletion is actually associated in increased psoriasis skin phenotype (210).The differences in long term vs. short term treatment may be linked to TRPA1 on other cell types, as additional studies have shown a role for TRPA1 on immune cells (71,(210)(211)(212).…”

Section: Trpa1mentioning

confidence: 99%

Involvement of Neural Transient Receptor Potential Channels in Peripheral Inflammation

et al. 2020

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Transient receptor potential (TRP) channels are a superfamily of non-selective cation channels that act as polymodal sensors in many tissues throughout mammalian organisms. In the context of ion channels, they are unique for their broad diversity of activation mechanisms and their cation selectivity. TRP channels are involved in a diverse range of physiological processes including chemical sensing, nociception, and mediating cytokine release. They also play an important role in the regulation of inflammation through sensory function and the release of neuropeptides. In this review, we discuss the functional contribution of a subset of TRP channels (TRPV1, TRPV4, TRPM3, TRPM8, and TRPA1) that are involved in the body's immune responses, particularly in relation to inflammation. We focus on these five TRP channels because, in addition to being expressed in many somatic cell types, these channels are also expressed on peripheral ganglia and nerves that innervate visceral organs and tissues throughout the body. Activation of these neural TRP channels enables crosstalk between neurons, immune cells, and epithelial cells to regulate a wide range of inflammatory actions. TRP channels act either through direct effects on cation levels or through indirect modulation of intracellular pathways to trigger pro-or antiinflammatory mechanisms, depending on the inflammatory disease context. The expression of TRP channels on both neural and immune cells has made them an attractive drug target in diseases involving inflammation. Future work in this domain will likely yield important new pathways and therapies for the treatment of a broad range of disorders including colitis, dermatitis, sepsis, asthma, and pain.

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“…104 In that study, no significant change in the mRNA expression of TRPV1 or TRPA1 in DRG cells was observed. 106 This indicates neuropeptides-ion channels signaling can induce cutaneous discomfort, but its role in psoriatic inflammation, either pro-inflammation or anti-inflammation, remains to be clarified. In parallel with that finding, histamine H1-receptor antagonists significantly inhibited spontaneous scratching on day 2, but not day 7.…”

Section: Ion Channels In the Pathogenesis Of Pruritus In Psomentioning

confidence: 99%

“…105 Intriguingly, another study using the same imiquimod murine model found that blockade, either genetic or pharmacological approaches, of common sensory neurogenic mechanisms for TRPV1, TRPA1, SP, and CGRP inhibits spontaneous biting/licking behaviors, which are indicative of cutaneous discomfort. 106 This indicates neuropeptides-ion channels signaling can induce cutaneous discomfort, but its role in psoriatic inflammation, either pro-inflammation or anti-inflammation, remains to be clarified.…”

Section: Ion Channels In the Pathogenesis Of Pruritus In Psomentioning

confidence: 99%

“…While inhibiting inflammation would generally reduce pruritus in AD and Pso, there is evidence that certain cytokine and neuropeptides-ion channels signaling can induce pruritus that is independent of inflammation in AD and Pso. 71,106,143 Curiously, there are AD patients who have generalized pruritus with no or minimal dermatitis. Current therapies are truly lacking to adequately manage these patients in which topical corticosteroids are not particularly effective.…”

Section: Con Clus Ionsmentioning

confidence: 99%

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Immune mediators and therapies for pruritus in atopic dermatitis and psoriasis

Zhou

et al. 2019

J Cutaneous Imm & Allergy

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractAtopic dermatitis (AD) and psoriasis (Pso) are two common inflammatory skin diseases which are symptomatically characterized by pruritus to variable degrees.Whereas AD is nearly always associated with pruritus, only 50%-70% of patients with Pso suffer from itching. Within the last decade, the development of biologic agents targeting specific cytokines or cytokine receptors has led to tremendous progress in suppressing inflammation (and thus improving quality of life) in these two diseases.While suppressing inflammation would generally reduce pruritus in these inflammatory diseases, pruritus is still recalcitrant for treatment in some patients due to relative lack of therapeutics that specifically inhibit pruritus signaling. There is abundant evidence that certain cytokines and neuropeptides-ion channels signaling mediate pruritus that is independent of inflammation in AD and psoriasis. Of note, Janus kinase (JAK) and nerve growth factor (NGF)-tropomyosin receptor kinase A (TrkA)transient receptor potential vanilloid 1 (TRPV1) signaling partially regulates pruritus in AD and psoriasis. JAK kinases inhibitors decrease the extent of itch in patients with AD and psoriasis. In clinical trials, topical inhibitors of TrkA and TRPV1 have been reported to reduce pruritus in patients with Pso and AD, respectively. In this article, we review recent literature knowledge regarding the mechanisms underlying pruritus in AD and Pso, providing hypotheses for why pruritus may be more common in AD than in Pso. In light of the different mechanisms underlying these two diseases, the current and developing therapeutics, either in human clinical trials or animal studies, for targeting pruritus are also discussed. K E Y W O R D SIL-31, neuropeptide, PAR2, SP, thymic stromal lymphopoietin, TRPA1, TRPV1

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Sensory nerves mediate spontaneous behaviors in addition to inflammation in a murine model of psoriasis

Cited by 36 publications

References 76 publications

Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasis and IL-1β/IL-23p40 production

Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasis and IL-1β/IL-23p40 production

Involvement of Neural Transient Receptor Potential Channels in Peripheral Inflammation

Immune mediators and therapies for pruritus in atopic dermatitis and psoriasis

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