Phenotype and function of circulating memory T cells in human vitiligo.


Journal

The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041

Informations de publication

Date de publication:
11 2020
Historique:
accepted: 30 01 2020
pubmed: 6 2 2020
medline: 15 5 2021
entrez: 4 2 2020
Statut: ppublish

Résumé

Vitiligo is a chronic inflammatory skin disorder characterized by the loss of melanocytes. While a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response is now well demonstrated in vitiligo, recent data suggest that the T-cell component could be more complex, involving different combinatorial T-cell subsets. To analyse the phenotype and function of circulating CD4 This is a monocentric, prospective, descriptive and exploratory study. Multiparametric flow cytometry analyses were performed to evaluate the surface expression of homing and T-cell-subset markers together with intracellular cytokine production in peripheral blood mononuclear cells from 60 patients with vitiligo, 25 patients with psoriasis and 28 healthy donors. Vitiligo peripheral blood circulating effector and central memory T cells expressed similar proportions of skin-homing markers. Decrease in the frequencies of circulating CD4 The decreased frequencies of circulating Th1/Tc1, Th17/Tc17 and Th1/Th17-Tc1/Tc17 cells suggest a possible migration of these T-cell subsets into the skin of patients with vitiligo. These could be targeted to prevent flares of the disease. What is already known about this topic? Vitiligo is a chronic inflammatory skin disorder associated with the loss of melanocytes. Vitiligo is characterized by a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response in the skin. What does this study add? A thorough analysis of the phenotype and function of circulating memory T cells suggests the migration of Th1/Tc1, Th17/Tc17 and Th1/Th17-Tc1/Tc17 cell subsets in the skin. What is the translational message? A better understanding of the different immune T-cell subsets involved in vitiligo could lead to better therapeutic options. Linked Comment: Matos. Br J Dermatol 2020; 183:803.

Sections du résumé

BACKGROUND
Vitiligo is a chronic inflammatory skin disorder characterized by the loss of melanocytes. While a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response is now well demonstrated in vitiligo, recent data suggest that the T-cell component could be more complex, involving different combinatorial T-cell subsets.
OBJECTIVES
To analyse the phenotype and function of circulating CD4
METHODS
This is a monocentric, prospective, descriptive and exploratory study. Multiparametric flow cytometry analyses were performed to evaluate the surface expression of homing and T-cell-subset markers together with intracellular cytokine production in peripheral blood mononuclear cells from 60 patients with vitiligo, 25 patients with psoriasis and 28 healthy donors.
RESULTS
Vitiligo peripheral blood circulating effector and central memory T cells expressed similar proportions of skin-homing markers. Decrease in the frequencies of circulating CD4
CONCLUSIONS
The decreased frequencies of circulating Th1/Tc1, Th17/Tc17 and Th1/Th17-Tc1/Tc17 cells suggest a possible migration of these T-cell subsets into the skin of patients with vitiligo. These could be targeted to prevent flares of the disease. What is already known about this topic? Vitiligo is a chronic inflammatory skin disorder associated with the loss of melanocytes. Vitiligo is characterized by a T helper cell (Th)1/cytotoxic T cell (Tc)1-skewed immune response in the skin. What does this study add? A thorough analysis of the phenotype and function of circulating memory T cells suggests the migration of Th1/Tc1, Th17/Tc17 and Th1/Th17-Tc1/Tc17 cell subsets in the skin. What is the translational message? A better understanding of the different immune T-cell subsets involved in vitiligo could lead to better therapeutic options. Linked Comment: Matos. Br J Dermatol 2020; 183:803.

Identifiants

pubmed: 32012221
doi: 10.1111/bjd.18902
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

899-908

Subventions

Organisme : ATIP-AVENIR
Organisme : Agence Nationale de la Recherche

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2020 British Association of Dermatologists.

Références

Picardo M, Dell'Anna ML, Ezzedine K et al. Vitiligo. Nat Rev Dis Primers 2015; 1:15011.
Boniface K, Seneschal J, Picardo M, Taieb A. Vitiligo: focus on clinical aspects, immunopathogenesis, and therapy. Clin Rev Allergy Immunol 2018; 54:52-67.
Frisoli ML, Harris JE. Vitiligo: mechanistic insights lead to novel treatments. J Allergy Clin Immunol 2017; 140:654-62.
Le Poole IC, Mehrotra S. Replenishing regulatory T cells to halt depigmentation in vitiligo. J Investig Dermatol Symp Proc 2017; 18:S38-45.
Harris JE, Harris TH, Weninger W et al. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8⁺ T-cell accumulation in the skin. J Invest Dermatol 2012; 132:1869-76.
Yang L, Wei Y, Sun Y et al. Interferon-γ inhibits melanogenesis and induces apoptosis in melanocytes: a pivotal role of CD8+ cytotoxic T lymphocytes in vitiligo. Acta Derm Venereol 2015; 95:664-70.
Rashighi M, Agarwal P, Richmond JM et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med 2014; 6:223ra23.
Boniface K, Jacquemin C, Darrigade A-S et al. Vitiligo skin is imprinted with resident memory CD8 T cells expressing CXCR3. J Invest Dermatol 2018; 138:355-64.
Jacquemin C, Martins C, Lucchese F et al. NKG2D defines a subset of skin effector memory CD8 T cells with pro-inflammatory functions in vitiligo. J Invest Dermatol 2020; DOI: 10.1016/j.jid.2019.11.013.
Jacquemin C, Rambert J, Guillet S et al. Heat shock protein 70 potentiates interferon alpha production by plasmacytoid dendritic cells: relevance for cutaneous lupus and vitiligo pathogenesis. Br J Dermatol 2017; 177:1367-75.
Bertolotti A, Boniface K, Vergier B et al. Type I interferon signature in the initiation of the immune response in vitiligo. Pigment Cell Melanoma Res 2014; 27:398-407.
Guttman-Yassky E, Krueger JG. Atopic dermatitis and psoriasis: two different immune diseases or one spectrum? Curr Opin Immunol 2017; 48:68-73.
Czarnowicki T, He H, Leonard A et al. Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases. J Allergy Clin Immunol 2019; 143:2095-107.
Richmond JM, Strassner JP, Zapata L et al. Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo. Sci Transl Med 2018; 10:eaam7710.
Matos TR, O'Malley JT, Lowry EL et al. Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αβ T cell clones. J Clin Invest 2017; 127:4031-41.
Taieb A, Picardo M. The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force. Pigment Cell Res 2007; 20:27-35.
Benzekri L, Gauthier Y. Clinical markers of vitiligo activity. J Am Acad Dermatol 2017; 76:856-62.
Sosa JJ, Currimbhoy SD, Ukoha U et al. Confetti-like depigmentation: a potential sign of rapidly progressing vitiligo. J Am Acad Dermatol 2015; 73:272-5.
Hudak S, Hagen M, Liu Y et al. Immune surveillance and effector functions of CCR10+ skin homing T cells. J Immunol 2002; 169:1189-96.
Kupper TS, Fuhlbrigge RC. Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol 2004; 4:211-22.
Park CO, Kupper TS. The emerging role of resident memory T cells in protective immunity and inflammatory disease. Nat Med 2015; 21:688-97.
Clark RA, Chong B, Mirchandani N et al. The vast majority of CLA+ T cells are resident in normal skin. J Immunol 2006; 176:4431-9.
Gehad A, Teague JE, Matos TR et al. A primary role for human central memory cells in tissue immunosurveillance. Blood Adv 2018; 2:292-8.
Watanabe R, Gehad A, Yang C et al. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. Sci Transl Med 2015; 7:279ra39.
Zhang L, Kang Y, Chen S et al. Circulating CCL20: a potential biomarker for active vitiligo together with the number of Th1/17 cells. J Dermatol Sci 2019; 93:92-100.
Zhen Y, Yao L, Zhong S et al. Enhanced Th1 and Th17 responses in peripheral blood in active non-segmental vitiligo. Arch Dermatol Res 2016; 308:703-10.
Elela MA, Hegazy RA, Fawzy MM et al. Interleukin 17, interleukin 22 and FoxP3 expression in tissue and serum of non-segmental vitiligo: a case-controlled study on eighty-four patients. Eur J Dermatol 2013; 23:350-5.
Zhou J, An X, Dong J et al. IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo. FASEB J 2018; 32:4899-916.
Speeckaert R, Mylle S, van Geel N. IL-17A is not a treatment target in progressive vitiligo. Pigment Cell Melanoma Res 2019; 31:330.
Czarnowicki T, He H, Krueger JG, Guttman-Yassky E. Atopic dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol 2019; 143:1-11.
Hamzavi I, Jain H, McLean D et al. Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index. Arch Dermatol 2004; 140:677-83.
van Geel N, Lommerts J, Bekkenk M et al. Development and validation of the Vitiligo Extent Score (VES): an international collaborative initiative. J Invest Dermatol 2016; 136:978-84.

Auteurs

C Martins (C)

INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.

A-S Darrigade (AS)

INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.
Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, Bordeaux, France.

C Jacquemin (C)

INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.

T Barnetche (T)

Department of Rheumatology, National Reference Center for Severe Systemic Auto-Immune Diseases, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.

A Taieb (A)

INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.
Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, Bordeaux, France.

K Ezzedine (K)

Department of Dermatology, AP-HP, Hôpital Henri-Mondor, Créteil, France.

K Boniface (K)

INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.
Fédération Hospitalo-Universitaire, ACRONIM, Bordeaux, France.

J Seneschal (J)

INSERM U1035, BMGIC, Immuno-Dermatology Team, University of Bordeaux, Bordeaux, France.
Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hôpital Saint-André, Bordeaux, France.
Fédération Hospitalo-Universitaire, ACRONIM, Bordeaux, France.

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