| Vitiligo is a common skin disease characterized by a chronic and progressive depigmention as a consequence of local melanocyte loss. Vitiligo is a multifactorial polygenic disorder with a complex interaction between genetic, environmental, biochemical and immunological events. Histological analysis of the perilesional margin surrounding the depigmented skin reveals a lymphocytic infiltrate consisting of activated CD4+T and CD8+T cells. Studies showed that increased expression of the MHC class II antigen HLA-DR and intercellular adhesion molecule-1(ICAM-1) by these T cells. In addition, these T cells were skin-homing, polarized toward type-1 effector function. Moreover, vitiligo patients often have circulating skin-homing melanocyte-specific cytotoxic T lymphocytes(CTL), and CTL are usually infiltrating close to the disappearing melanocytes.CD4+CD25+ regulatory T cell(Treg cell) is a kind of T cell subsets with imm play a key role in immunosuppressive functions. In vitiligo, a limited number of Treg is found not only in lesional, but also in non-lesional and peri-lesional vitiligo skin. In addition, these Treg displayed reduced ability to hold local immune responses. Recently, studies suggested that in vitiligo animal model, the depigmentation could be suppressed by adoptive transfer of Treg cells, enhanced Treg function by rapamycin, or enhanced expression of CCL22 which promote Treg skin homing. These findings suggest that enhanced Treg number or function may be used for the treatment of vitiligo.At present, there are no Drug Administration–approved treatments for vitiligo. Clinically, narrow band-ultraviolet B(NB-UVB) is widely used due to its satisfactory results and little side effect. However,the mechanism of NB-UVB for the treatment of vitiligo is still not clear. Previous studies have reported that skin irradiation of NB-UVB induce expression of chemokines, therefore contribute to skin migration of immune cells. We thus hypothesized that NB-UVB induce expression of CCL22, which can promote Treg skin homing to suppress depigmentation in vitiligo.Objective: This study intends to explore the role of NB-UVB on the chemokines CCL22 expression in keratinocytes.Methods: 1. Ha Ca T cell line was cultured and exposure to different dose of NB-UVB(0, 100, 200, 400 m J/cm2) irradiation, CCL22 m RNA and protein secretion were detected by real-time PCR and ELISA at indicated time points;2. Ha Ca T cells were exposed to different doses of NB-UVB(0, 100, 200, 400 m J/cm2) irradiation; the possible signaling pathway involved in CCL22 expression(including NF-k B p65, Phospho- NF-k B p65) were detected by Western-blot;3. Ha Ca T cells were pretreated by PDTC(inhibitor of NF-k B signailing pathway) and then exposured to NB-UVB(400 m J/cm2) irradiation, CCL22 expression were detected by real-time PCR and ELISA.Results: 1. Both RT-PCR and ELISA results showed that NB-UVB could induce the CCL22 m RNA level and secretion in Ha Ca T by NB-UVB irradiation in a dose- and time-dependent manner;2. Western-blot results showed after 2 hours NB-UVB irradiation, the phosphorylation of NF-?B p65 were significantly increased in a does-dependent manner;3. Both RT-PCR and ELISA results showed that pretreatment of Ha Ca T cells with PDTC significantly reduced the CCL22 m RNA and secretion level induced by NB-UVB.Conclusion: In this study, we firstly clarify that NB-UVB could induce expression and secretion of chemokine CCL22 via NF-?B pathway in keratinocytes. Thus, we can infer that NB-UVB may induce CCL22 expression and contribute to the skin migration of Treg cells, therefore suppress the local autoimmune response and depigmentation. |
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