Vitiligo is an autoimmune disease of the skin that results in the destruction of melanocytes and the clinical appearance of white spots. Disease pathogenesis depends on IFN-γ and IFN-γ-induced chemokines to promote T cell recruitment to the epidermis where melanocytes reside. The skin is a complex organ, with a variety of resident cell types. We sought to better define the microenvironment and distinct cellular contributions during autoimmunity in vitiligo, and found that the epidermis is a chemokine-high niche in both a mouse model and human vitiligo. Analysis of chemokine expression in mouse skin revealed that CXCL9 and CXCL10 expression strongly correlate with disease activity, whereas CXCL10 alone correlates with severity, supporting them as potential biomarkers for following disease progression. Further studies in both our mouse model and human patients revealed that keratinocytes were the major chemokine-producers throughout the course of disease, and functional studies using a conditional STAT1 knockout mouse revealed that IFN-γ signaling in keratinocytes was critical for disease progression and proper autoreactive T cell homing to the epidermis. In contrast, epidermal immune cell populations including endogenous T cells, Langerhans cells, and γδ T cells were not required. These results have important clinical implications, as topical therapies that target IFN-γ signaling in keratinocytes could be safe and effective new treatments, and skin expression of these chemokines could be used to monitor disease activity and treatment responses.
Background
Histopathological features in morphea (localized scleroderma) and their clinical correlates are poorly described.
Objective
Systematically describe histologic changes of morphea in a large, well annotated cohort and determine the association between histopathology and clinical features.
Methods
Cross-sectional study of 83 patients enrolled in the Morphea in Adults and Children (MAC) cohort. The main outcome measure was the association of microanatomical location and degree of sclerosis and inflammation seen on histologic samples with patient reported symptoms and physician-based measures of severity.
Results
Pattern of sclerosis was associated with morphea subtype, the presence of patient reported symptoms, and functional limitation. A bottom heavy pattern of sclerosis was associated with pain and tightness (P = 0.0039, 0.001 respectively). These symptoms were not associated with a top heavy pattern. Severe inflammation may be associated with pain and functional limitation (p = 0.073 for both).
Limitations
Small sample size limits ability to detect associations, particularly in subgroups.
Conclusions
Histopathological examination of morphea may assist in identifying patients who may require additional monitoring and treatment. Features such as patterns of sclerosis and severity of inflammation should be included in pathology reports to help aid in clinical management.
Blister grafting is successful in most patients with vitiligo, with a high graft survival rate; however, the degree of pigment spread is variable and depends on clinical characteristics of the patient and graft site.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.