Altered circulating memory T cells in vitiligo cases followed NB-UVB therapy.

BACKGROUND: Vitiligo represents a commonly diagnosed autoimmune disease caused by the depletion of epidermal melanocytes. Many subsets of T cells contribute to vitiligo pathogenesis, including resident and circulating memory T cells. OBJECTIVES: To analyze the amounts of CD4+ and CD8+ memory T-cell subsets in peripheral blood specimens from vitiligo patients and alterations caused by narrowband ultraviolet B (NB-UVB) phototherapy. METHODS: Circulating CD4+ and CD8+ central memory T (TCM ) and effector memory T (TEM ) cell frequencies in 33 patients with non-segmental vitiligo and 16 healthy donors were evaluated by flow cytometry. Related chemokine levels were also detected. RESULTS: Peripheral blood CD4+ TCM and CD8+ TCM counts were markedly reduced in vitiligo cases while they were higher in active vitiligo compared with stable vitiligo cases. Circulating CD8+ TCM frequency in vitiligo was closely related to disease duration. Interestingly, CD4+ TCM and CD8+ TCM frequencies, alongside CXCL9 and CXCL10 amounts in peripheral blood of patients with vitiligo, were significantly decreased after NB-UVB phototherapy. CONCLUSIONS: Decreased frequencies of circulating CD4+ TCM and CD8+ TCM by NB-UVB suggest a possible immunosuppressive effect of phototherapy. The chemokines CXCL9 and CXCL10 are the bridge between circulating and skin resident memory T cells. NB-UVB blocks the homing of circulating memory T cells into vitiligo lesions by down-regulating CXCL9 and CXCL10. Targeting the above proteins could provide novel, durable treatment options to cure and prevent flares of this disease.

Role of chemokines and the corresponding receptors in vitiligo: A pilot study.

To determine the levels and sources of chemokines in the serum and epidermis of vitiligo patients, we examined 80 active patients, 80 stable patients and 40 healthy controls. First, the serum levels of candidate chemokines were measured by Luminex assay, and levels of CCR5, CXCR1 and CXCR3 were measured in peripheral mononuclear cells (PMBC) by flow cytometry. Then, the local epidermis levels of elevated chemokines in vitiligo were tested by Luminex. Finally, the mRNA and protein expression levels of elevated chemokines in HaCaT cells stimulated with interferon (IFN)-γ or tumor necrosis factor (TNF)-α were tested by quantitative real-time polymerase chain reaction and Luminex. The serum levels of CCL5, CXCL8 and CXCL10 in active vitiligo were significantly elevated compared with those in stable vitiligo patients. Furthermore, the levels of CCL3 and CCL4 had weak and positive correlations with the Vitiligo Area Scoring Index. In the peripheral blood of active vitiligo patients, the percentages of CD3+ CD8+ CCR5+ and CD3+ CD8+ CXCR3+ T cells were significantly increased compared with those in stable vitiligo and healthy controls. In the epidermis of lesions, the expression levels of CCL5 and CXCL10 in active vitiligo were significantly increased. In addition, the mRNA and protein levels of CCL5, CXCL8 and CXCL10 were significantly elevated in HaCaT cells after stimulation with TNF-α or IFN-γ. The CCR5/CCL5 and CXCR3/CXCL10 axes may play an important role in the progression and maintenance of vitiligo. Moreover, keratinocytes stimulated with TNF-α and IFN-γ may be a primary source of CCL5 and CXCL10.