Mast cell-derived chemokine C-C motif ligand 5 affects the migration of CD8 + T cells from vitiligo patients under oxidative stress
- VernacularTitle:肥大细胞来源的趋化因子配体5影响氧化应激状态下白癜风CD8 + T细胞的迁移
- Author:
Pu SONG
1
;
Yu LIU
1
;
Sen GUO
1
;
Shuli LI
1
;
Ling LIU
1
;
Chunying LI
1
Author Information
- Publication Type:Journal Article
- Keywords: Vitiligo; Mast cells; Leukocytes, mononuclear; Chemokine CCL5; CD8-positive T-lymphocytes
- From: Chinese Journal of Dermatology 2025;58(9):839-843
- CountryChina
- Language:Chinese
- Abstract: Objective:To investigate the effect of mast cell-derived chemokine C-C motif ligand 5 (CCL5) on the migration of CD8 + T cells from vitiligo patients under oxidative stress conditions. Methods:From January 2017 to January 2023, 10 patients with progressive segmental vitiligo, 10 patients with non-segmental vitiligo, and 10 healthy individuals were collected from the Department of Dermatology, Xijing Hospital. Skin tissue samples were obtained from the lesions of vitiligo patients and from the normal skin of healthy individuals, with sampling sites including the face, neck, and upper extremities, and toluidine blue staining was performed to analyze the characteristics of mast cells infiltrating the skin lesions. The effect of H 2O 2 treatment on mast cells was investigated in Transwell chambers. Peripheral blood mononuclear cells (PBMCs) from vitiligo patients were added to the upper chamber, while the human mast cell line LAD2 was added to the lower chamber and divided into 4 groups to receive different treatments: untreated group receiving no special treatment, H 2O 2 group pretreated with H 2O 2, H 2O 2 + neutralization antibody group pretreated with H 2O 2 followed by the treatment with CCL5/RANTES-neutralizing antibodies, and H 2O 2 + PF group pretreated with H 2O 2 followed by the treatment with a Janus kinase 3/non-receptor protein tyrosine kinase selective inhibitor PF-06651600. After 6 hours of co-incubation, cell suspensions were collected from the lower chamber. The number of CD8 + T cells was counted using flow cytometry, and the CCL5 level in the cell culture supernatant was detected using enzyme-linked immunosorbent assay. One-way analysis of variance was used to analyze differences among groups, and least significant difference- t test was used for multiple comparisons. Pearson correlation analysis was performed for correlation analysis. Results:In the 200 × magnification field, the numbers of infiltrating mast cells significantly differed among segmental vitiligo lesions, non-segmental vitiligo lesions, and normal skin tissues (15.7 ± 3.3, 20.9 ± 3.9, 7.2 ± 2.9, respectively; F = 8.07, P = 0.002) ; additionally, the number of infiltrating mast cells was significantly higher in the segmental or non-segmental vitiligo lesions than in the normal skin tissues (LSD- t = 3.50, 5.70, P = 0.047, 0.001, respectively), but there was no significant difference between the segmental and non-segmental vitiligo lesions (LSD- t = 2.20, P = 0.293). A significant positive correlation was observed between the number of infiltrating mast cells and that of CD8 + T cells in the vitiligo lesions ( r = 0.82, P = 0.004). The numbers of CD8 + T cells and CCL5 levels significantly differed among the untreated group, H 2O 2 group, H 2O 2 + neutralization antibody group, and H 2O 2 + PF group (CD8 + T cells: 197.0 ± 45.9, 580.4 ± 62.6, 296.0 ± 43.2, 398.6 ± 62.8, respectively; CCL5: 2.2 ± 0.6 pg/ml, 9.9 ± 1.3 pg/ml, 3.4 ± 0.4 pg/ml, 6.33 ± 0.7 pg/ml, respectively; F = 11.03, 17.77, respectively, both P < 0.001) ; additionally, the H 2O 2 group showed significantly increased numbers of CD8 + T cells and CCL5 levels compared with the untreated group, H 2O 2 + neutralization antibody group, and H 2O 2 + PF group (all P < 0.05) . Conclusion:Mast cells may be involved in the pathogenesis of vitiligo under oxidative stress, and mast cell-derived CCL5 appears to contribute to the occurrence and development of vitiligo by affecting CD8 + T cell migration.
