Tissue-resident Memory T Cells Expression Among the Repigmentation Patterns Induced by NB-UVB Phototherapy in Vitiligo

Study Overview
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Brief Summary
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Vitiligo is the most commonly acquired depigmentation disorder characterized by selective destruction of melanocytes resulting in well-circumscribed achromic macules. Tissue-resident memory T cells (TRM) are memory T lymphocyte subsets that reside in the skin, lack recirculation, proliferate locally, produce cytokines, and may be implicated in relapses. NB-UVB Phototherapy induces repigmentation in certain patterns. The aim of this study was to determine the levels of TRM cells on vitiligo lesions, and after phototherapy by repigmentation pattern.

Detailed Description
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Vitiligo is the most commonly acquired depigmentation disorder characterized by the selective destruction of melanocytes. Its etiology is not yet fully understood, but the most accepted hypotheses are genetic predisposition, environmental factors, oxidative stress and immune response. In relation with the latter, the damage-associated molecular patterns activate TRM cells and induce interferon-gamma that release CXCL9/10, recruiting cytotoxic CD8+ that ultimately destroys melanocytes. Furthermore, the lesions recur 40% in the first year and in the same site, suggesting local autoimmune response by TRM cells. The TRM cells are memory T lymphocyte subsets that reside in the skin, lack recirculation, proliferate locally, and produce cytokines. TRM cells express the CD69+CD103+ surface markers. Moreover, TRM cells express specific transcription factors like Hobbit, Blimp1, Runx3 and Notch1, which regulate their differentiation and survival. Interleukin (IL)-15 stimulates Hobbit, which drives TRM cells long-term maintenance by blocking CCR7-S1PR1 and promoting the expression of CD103+. Blimp1 is essential for the differentiation of TRM cells, as it inhibits the differentiation of naive T cells into circulating-memory T cells, and regulates the effector function by stimulating granzyme B and promoting the expression of CD69+. Runx3 is essential for TRM cells long-term maintenance by promoting CD103+, which can also induce Blimp1 and Hobbit. Notch1 is essential for the maintenance of CD103+, facilitating the TRM-epithelium linking. Both TRM cells and central-memory T cells have been found in vitiligo lesions, and the CD69+CD103+ TRM cells are increased in vitiligo skin. NB-UVB phototherapy is the first line treatment for vitiligo involving more than 10 percent of the body surface area, with an average response rate of 67%. It promotes repigmentation by differentiation and migration of perilesional melanocytes, tyrosinase increase and inhibition of effector and memory T cells. NB-UVB promotes different patterns of repigmentation such as follicular, marginal, and diffuse. The NB-UVB exposure causes a decrease in the transforming factor beta that maintain the expression of CD103+, but there is no data about the CD69+ modification, suggesting a possible effect on TRM cells. Vitiligo relapses tend to be at the same site of previous lesions, suggesting local autoimmunity by the TRM cells that could be modified by UVB-NB phototherapy. Phototherapy can inhibit effector and memory-T cells; however its effect on TRM cells in vitiligo and their modification is unknown. The purpose of this study was to determine the levels of TRM cells on vitiligo lesions, and following NB-UVB phototherapy by repigmentation pattern.

Official Title
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Tissue-resident Memory T Cells Expression Among the Repigmentation Patterns Induced by NB-UVB Phototherapy in Vitiligo

Conditions
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Vitiligo

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Symmetric vitiligo Affected body surface greater than 10% Patients with follicular, marginal and diffuse repigmenting patterns No previous topical or systemic treatment in the previous 2 and 3 months, respectively Signed informed consent Exclusion Criteria: Concomitant treatment or systemic diseases Pregnancy Drugs intake Mental disorders Acral, universal or segmental vitiligo

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Vitiligo vulgaris<br>A serial of vitiligo patients under treatment with UVB-NB | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue-resident memory T cells | To quantify the expression of Tissue-resident memory T cells before and after phototherapy | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue-resident memory T cells among the repigmentation patterns | To quantify the expression of Tissue-resident memory T cells among the repigmentation patterns induced by NB-UVB phototherapy | Up to 1 year | 
| Arrangment of the Tissue-resident memory T cells among the repigmentation patterns | To show and quantify the fluorescence intensity of the CD69+CD103+ TRM cells among the repigmentation patterns induced by NB-UVB phototherapy | Up to 1 year | 
| TRM transcriptional factors profile | To quantify the TRM transcriptional factors expression in lesional skin and between the repigmentation patterns. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hobbit, vitiligo, Ultraviolet Therapy, Pigmentation, Tissue-resident memory T cells, Blimp1, Runx3, Notch1