214 Increased cutaneous activation of innate immunity and pro-apoptotic CXCR3B in patients with segmental vitiligo

Abstract

Segmental vitiligo (SV) is a rare form of vitiligo, characterized by white patchy skin due to destruction of melanocytes affecting only one side of the body. The mechanisms are poorly understood. Recently we have demonstrated the importance of innate immunity and a newly discovered melanocytic chemokine receptor CXCR3B in triggering early anti-melanocytic response in non-segmental or generalized vitiligo. The role of innate immunity or CXCR3B in SV has not been studied. To do this, we obtained 2x4-mm skin biopsies from normal-appearing skin of SV patients (n=5), one from a non-depigmented skin of the affected side of the body (L) and the second from the contralateral non-effected side of the same patient (NL) and results were compared to healthy controls matched from age and biopsy location (n=5). Biopsies were cut in 2 for PCR and immunofluorescent staining. Our results have shown increased expression of vitiligo signature cytokines (IFNg) and chemokines (CXCL9 and CXCL10) as well as markers of ECM disruption (increased MMP-9 and decreased E-cadherin) in both L and NL sites. The targets of cellular stress (CXCL16, iHSP70) and cellular damage (mito-DNA) were only increased in L but not in NL sites. We found a significant increase in CXCR3B mRNA at both sites and a significantly increased number of CXCR3B+ melanocytes at L sites only, which may explain their increased responses to chemokines. In conclusion, our results suggest that SV patients, as has been described for NSV, have increased innate immunity throughout their skin which precedes depigmentation. Increased CXCR3B expression in SV suggests strategies fighting against the local stress or specifically targeting CXCR3B activation could provide effective approaches for halting the progression of this disabling disease.