Pleiotropic Role of TRPV1 in Psoriasis Inflammation

Study Overview
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Brief Summary
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Widely expressed in the sensory nerve endings of the skin, Transient Receptor Potential Vanilloid 1 (TRPV1) is a receptor that plays an important role in the perception of pain and pruritus but also in skin inflammation, primarily by inducing the local release of several neuropeptides. Although the mechanisms by which TRPV1-sensitizing inflammatory mediators in damaged skin have received considerable attention, the role of TRPV1 in psoriasis has so far been little explored. However, two studies have reported that ablation of sensory nerves expressing TRPV1 reduced psoriasiform skin inflammation, demonstrating the neuronal contribution to inflammation in psoriasis. However, the expression of TRPV1 is not limited to neurons alone. TRPV1 is also expressed by epidermal keratinocytes and skin microvessels. For example, in 2018, transcriptomic analysis of psoriatic patient skins (by definition devoid of neuron nuclei) revealed that TRPV1 expression was increased in the skin of psoriatic patients suffering from itching (pruritus). Regarding human keratinocytes, it is recognized that the activation of TRPV1 present on their surface induces the release of pro-inflammatory factors such as cyclooxygenase-2. In addition, the investigators have demonstrated that TRPV1 has a pivotal role in the keratinocyte production of inflammatory mediators, which is mediated by the protease-activated receptor-2 (PAR-2). However, the role of vascular TRPV1 in inflammation is not described. The investigators hypothesize that in addition to neuronal TRPV1, non-neuronal TRPV1 receptors of non-neuronal cells (keratinocytes and endothelial cells) may be involved in the vicious circle of the inflammatory process characteristic of psoriasis. Putting TRPV1 at the center of the deregulation of the homeostatic balance including epithelial, neuronal and vascular inflammation in psoriasis is totally innovative.

Detailed Description
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Each patient will have a sample taken in the dermatology department: 4 skin biopsies A blood sample. Patients with psoriasis will be recruited from the dermatology department. There will be no further visits, so the duration of the study is 1 day. The samples taken will be used to determine the pleiotropic role of TRPV1 in Psoriasis Inflammation.

Official Title
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Pleiotropic Role of TRPV1 in Psoriasis Inflammation

Conditions
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Inflammation; Skin, Psoriasis

Intervention / Treatment
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* Procedure: skin biopsy and blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years old with psoriasis, with or without itching (pruritus). Presence of lesional and non lesional zones, in unexposed areas and surface area (outside the face and folds) large enough to allow the biopsies to be performed Patients who have given written consent Exclusion Criteria: Patients with physical or psychological incapacity to sign consent Patients not covered by the Social Security system Patients with topical treatments for psoriasis, Patients with systemic treatments for psoriasis, Patients allergic to lidocaine Patients over the age of majority who are subject to legal protection or who are unable to give consent Patients deprived of liberty by a judicial or administrative decision Pregnant women, parturients and breastfeeding mothers

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All patients<br>All patients with psoriasis recruted by dermatological departement. | Procedure: skin biopsy and blood sampling<br>* 4 skin biopsies outside the face under local anesthesia: 2 in damaged zone, 2 in non-damage zone. A blood sample<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Role of TRPV1 receptors expressed by sensory neurons and non-neuronal cells (keratinocytes and endothelial cells) in the inflammatory process characteristic of psoriasis. | Density of intra-epidermal nerve fibers expressing the TRPV1 receptor | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Density changes of intra-epidermal nerve fibers expressing neuropeptides | Density of intra-epidermal nerve fibers expressing neuropeptides by immunohistochemistry | 1 day | 
| Changes in endothelial cell density between an injured and an uninjured area of the same patient | quantification of the transcriptional and protein expression of TRPV1 | 1 day | 
| Changes in endothelial cell density between an injured and an uninjured area of the same patient | quantification of TRPV1 activity | 1 day | 
| Changes in endothelial cell density between an injured and an uninjured area of the same patient | Identification and quantification of the blood cytokine profile | 1 day | 
| Changes in the density of keratinocytes and their contacts with nerve fibers | Number and distribution of contacts between keratinocytes and nerve fibers | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, TRVP1