Background In patients with vitiligo, an increased reactive oxygen species (ROS) level has been proved to be a key player during disease initiation and progression in melanocytes. Nevertheless, ...little is known about the effects of ROS on other cells involved in the aberrant microenvironment, such as keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and was recently found to mediate homing of CD8+ T cells in human skin. Objective We sought to explicate the effect of oxidative stress on human keratinocytes and its capacity to drive CD8+ T-cell trafficking through CXCL16 regulation. Methods We first detected putative T-cell skin-homing chemokines and ROS in serum and lesions of patients with vitiligo. The production of candidate chemokines was detected by using quantitative real-time PCR and ELISA in keratinocytes exposed to H2 O2 . Furthermore, the involved mediators were analyzed by using quantitative real-time PCR, Western blotting, ELISA, and immunofluorescence. Next, we tested the chemotactic migration of CD8+ T cells from patients with vitiligo mediated by the CXCL16-CXCR6 pair using the transwell assay. Results CXCL16 expression increased and showed a positive correlation with oxidative stress levels in serum and lesions of patients with vitiligo. The H2 O2 -induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways: kinase RNA (PKR)–like ER kinase–eukaryotic initiation factor 2α and inositol-requiring enzyme 1α–X-box binding protein 1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6+ CD8+ T cells derived from patients with vitiligo. CXCR6+ CD8+ T-cell skin infiltration is accompanied by melanocyte loss in lesions of patients with vitiligo. Conclusion Our study demonstrated that CXCL16-CXCR6 mediates CD8+ T-cell skin trafficking under oxidative stress in patients with vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least in part, caused by unfolded protein response activation.
CRS with NP was defined by endoscopy findings of bilateral polyps originating from the middle meatus and/or confirmation of NP by computerized tomography.\n5 ± 16.4 37.2 ± 11.8 26.7 ± 14.5 29.5 ± ...17.1 32.7 ± 21.2 29.9 ± 20.1 Duration (y), mean ± SD 6.4 ± 5.2 5.8 ± 5.6 10.3 ± 5.6 8.4 ± 4.2 9.1 ± 8.4 11.1 ± 5.5 Sex       Male 4 107 22 830 17 962 Female 2 87 14 508 11 411 Smoking status (%)       Nonsmoking 3 125 20 655 13 843 Smoking 3 69 16 683 15 530 low *Atopic status (%) 6 (100) 74 (38.1) 31 (86.1) 505 (36.8) UA UA low *Tissue eosinophils (/HPF), mean ± SD 12.9 ± 4.2 2.9 ± 1.1 UA UA UA UA low *Blood eosinophils (109/L), mean ± SD 0.24 ± 0.04 0.10 ± 0.02 0.26 ± 0.03 0.09 ± 0.01 UA UA Pulmonary function tests, mean ± SD       PEF pre-BD (L/min) 371 ± 65 UA 379 ± 87 UA UA UA PEF post-BD (L/min) 430 ± 74 UA 435 ± 94 UA UA UA FEV1 pre-BD (L) 2.6 ± 0.7 UA 2.6 ± 0.8 UA UA UA FEV1 pre-BD (% predicted) 86 ± 14 UA 84 ± 11 UA UA UA FEV1 post-BD (L) 3.0 ± 0.9 UA 3.1 ± 0.5 UA UA UA FEV1% change after BD 10 ± 12 UA 11 ± 15 UA UA UA Table I The sociodemographic and clinical characteristics of patients with CRS BD, Bronchodilator; HPF, high-power field; PEF, peak expiratory flow; UA, unavailable.Group I: patients with CRS for prospective study (n = 200); group II: patients with CRS for retrospective study (n = 1374); group III: patients with CRS for survey study for asthma progression (n = 1401). Characteristics Asthma with CRS Asthma without CRS N 12 188 Age (y), mean ± SD 48.5 ± 21.4 41.8 ± 19.7 Duration (y), mean ± SD 8.4 ± 7.2 5.5 ± 4.9 Sex   Male 7 111 Female 5 77 Smoking status (%)   Nonsmoking 4 59 Smoking 8 129 Atopic status, positive, n (%) 6 (50) 85 (45.2) Blood eosinophils (109/L) 0.23 ± 0.06 0.22 ± 0.05 Pulmonary function tests, mean ± SD   PEF pre-BD (L/min) 378 ± 95 365 ± 88 PEF post-BD (L/min) 441 ± 69 430 ± 81 FEV1 pre-BD (L) 2.6 ± 0.4 2.5 ± 0.5 FEV1 pre-BD (% predicated) 88 ± 11 84 ± 12 FEV1 post-BD (L) 3.0 ± 0.6 3.1 ± 0.4 FEV1% change after BD 13 ± 16 15 ± 17 Table I The sociodemographic and clinical characteristics of patients with CRS BD, Bronchodilator; HPF, high-power field; PEF, peak expiratory flow; UA, unavailable.Group I: patients with CRS for prospective study (n = 200); group II: patients with CRS for retrospective study (n = 1374); group III: patients with CRS for survey study for asthma progression (n = 1401).
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