Tissue-resident Memory T Cells Expression Among the Repigmentation Patterns Induced by NB-UVB Phototherapy in Vitiligo
NCT ID: NCT05506995
Last Updated: 2022-08-18
Study Results
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Basic Information
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COMPLETED
11 participants
OBSERVATIONAL
2021-08-01
2022-08-03
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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CASE_ONLY
PROSPECTIVE
Study Groups
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Vitiligo vulgaris
A serial of vitiligo patients under treatment with UVB-NB
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* 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
* Pregnancy
* Drugs intake
* Mental disorders
* Acral, universal or segmental vitiligo
18 Years
ALL
No
Sponsors
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Universidad Autonoma de San Luis Potosí
OTHER
Responsible Party
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Juan Pablo Castanedo-Cazares
Clinical and research professor in Dermatology
Principal Investigators
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Juan P Castanedo-Cazares, MD
Role: PRINCIPAL_INVESTIGATOR
Universidad Autonoma de San Luis Potosi
Locations
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Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"
San Luis Potosí City, , Mexico
Countries
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References
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Bae JM, Jung HM, Hong BY, Lee JH, Choi WJ, Lee JH, Kim GM. Phototherapy for Vitiligo: A Systematic Review and Meta-analysis. JAMA Dermatol. 2017 Jul 1;153(7):666-674. doi: 10.1001/jamadermatol.2017.0002.
Fraczek A, Owczarczyk-Saczonek A, Placek W. The Role of TRM Cells in the Pathogenesis of Vitiligo-A Review of the Current State-Of-The-Art. Int J Mol Sci. 2020 May 18;21(10):3552. doi: 10.3390/ijms21103552.
Riding RL, Harris JE. The Role of Memory CD8+ T Cells in Vitiligo. J Immunol. 2019 Jul 1;203(1):11-19. doi: 10.4049/jimmunol.1900027.
Richmond JM, Strassner JP, Rashighi M, Agarwal P, Garg M, Essien KI, Pell LS, Harris JE. Resident Memory and Recirculating Memory T Cells Cooperate to Maintain Disease in a Mouse Model of Vitiligo. J Invest Dermatol. 2019 Apr;139(4):769-778. doi: 10.1016/j.jid.2018.10.032. Epub 2018 Nov 10.
Behr FM, Chuwonpad A, Stark R, van Gisbergen KPJM. Armed and Ready: Transcriptional Regulation of Tissue-Resident Memory CD8 T Cells. Front Immunol. 2018 Jul 30;9:1770. doi: 10.3389/fimmu.2018.01770. eCollection 2018.
Mackay LK, Minnich M, Kragten NA, Liao Y, Nota B, Seillet C, Zaid A, Man K, Preston S, Freestone D, Braun A, Wynne-Jones E, Behr FM, Stark R, Pellicci DG, Godfrey DI, Belz GT, Pellegrini M, Gebhardt T, Busslinger M, Shi W, Carbone FR, van Lier RA, Kallies A, van Gisbergen KP. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science. 2016 Apr 22;352(6284):459-63. doi: 10.1126/science.aad2035.
Zubair R, Hamzavi IH. Phototherapy for Vitiligo. Dermatol Clin. 2020 Jan;38(1):55-62. doi: 10.1016/j.det.2019.08.005. Epub 2019 Oct 18.
Castanedo-Cazares JP, Cortes-Garcia JD, Fuentes-Ahumada C, Martinez-Rosales K, Torres-Alvarez B. Repigmentation patterns induced by NB-UVB and their relationship with melanocytic migration and proliferation in vitiligo. Photodermatol Photoimmunol Photomed. 2016 Sep;32(5-6):269-275. doi: 10.1111/phpp.12275. Epub 2016 Oct 5.
Patra V, Laoubi L, Nicolas JF, Vocanson M, Wolf P. A Perspective on the Interplay of Ultraviolet-Radiation, Skin Microbiome and Skin Resident Memory TCRalphabeta+ Cells. Front Med (Lausanne). 2018 May 30;5:166. doi: 10.3389/fmed.2018.00166. eCollection 2018.
Azzolino V, Zapata L Jr, Garg M, Gjoni M, Riding RL, Strassner JP, Richmond JM, Harris JE. Jak Inhibitors Reverse Vitiligo in Mice but Do Not Deplete Skin Resident Memory T Cells. J Invest Dermatol. 2021 Jan;141(1):182-184.e1. doi: 10.1016/j.jid.2020.04.027. Epub 2020 May 25. No abstract available.
Other Identifiers
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63-21
Identifier Type: -
Identifier Source: org_study_id
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