title: A similar local immune and oxidative stress phenotype in vitiligo and halo nevus.
abstract: BACKGROUND
  Vitiligo and halo nevus are two common T-cell-mediated skin disorders. Although autoimmunity has been suggested to be involved in both diseases, the relationship between vitiligo and halo nevus is not fully understood.
  
  
  OBJECTIVE
  The aim of the current study was to investigate whether vitiligo and halo nevus share the same immunological and oxidative stress response.
  
  
  METHODS
  Infiltrations of T cells, and expressions of chemokine receptors (CXCR3, CCR4, CCR5) and cytotoxic markers (Granzyme B, Perforin) in the lesions of vitiligo and halo nevus were examined by immunohistochemistry. Enzyme-linked immunosorbent assay was performed to analyze the expressions of chemokines in the serum samples and cytotoxic markers secreted by CD8+T cells which were sorted from the peripheral blood mononuclear cells in healthy donors, vitiligo and halo nevus patients. Tissue levels of chemokine receptors and CXCR3 ligands in healthy controls, vitiligo patients and halo nevus patients were determined by qRT-PCR analysis. The percentages of CXCR3+CD4+T and CXCR3+CD8+T cells from the peripheral blood samples were examined by flow cytometry. Tissue and serum hydrogen peroxide (H2O2) concentrations were measured using H2O2assay kit.
  
  
  RESULTS
  Immunohistochemistry revealed a significant T-cell response, with pronounced dermal infiltrates of CD8+T cells in vitiligo and halo nevus. The inflammatory cytotoxic markers such as Granzyme B and Perforin were also elevated in vitiligo and halo nevus, suggesting inflammatory responses in situ. By qRT-PCR and ELISA assay, we found significantly increased expressions of the chemokine receptor CXCR3 and its ligands, especially the accumulated CXCL10 in the skin lesions of vitiligo and halo nevus. Moreover, the level of H2O2, a key player involved in regulation of the immune response was significantly upregulated in the skin lesions of vitiligo and halo nevus. In addition, the increased H2O2concentration correlated positively with CXCL10 level in skin lesions of vitiligo and halo nevus.
  
  
  CONCLUSIONS
  These results demonstrate a H2O2-involved autoimmune phenotype in vitiligo and halo nevus, characterized by increased level of IFN-γ-inducible chemokine pair CXCL10-CXCR3, as well as a dense CD8+T infiltration in the skin lesions, thus suggesting a similar pathogenesis of the two diseases.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: wanglin@fmmu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, No. 127 Changlexi Road, Xi'an 710032, Shaanxi, China. Electronic address: xjzhejian@fmmu.edu.cn.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jian
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054357:Chemokine CXCL10 / Q000032:analysis; D006801:Humans; D055882:Nevus, Halo / Q000276:immunology* / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000032:analysis; D012867:Skin / Q000473:pathology; D014820:Vitiligo / Q000276:immunology* / Q000378:metabolism
chemical_list: C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D017382:Reactive Oxygen Species; D054367:Receptors, CXCR3
keywords: CD8(+) T cells; CXCL10; CXCR3; Halo nevus; Oxidative stress; Vitiligo