Increased expression of
            <scp>CXCR</scp>
            3 and its ligands in patients with vitiligo and
            <scp>CXCL</scp>
            10 as a potential clinical marker for vitiligo

Wang, X. X.; Wang, Qianqian; Wu, Jinfeng; Jiang, Min; Chen, L.; Zhang, C. F.; Xiang, Leihong

doi:10.1111/bjd.14416

Cited by 141 publications

(100 citation statements)

References 46 publications

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“…In a recent study that examined a large number of vitiligo patients, serum levels of CXCL9 and CXCL10 correlated with disease activity, while only CXCL10 reflected disease severity (Wang et al , 2016), and another study reported low-level expression of CXCL10 in stable lesions (Regazzetti et al , 2015). Therefore, targeting both CXCL9 and CXCL10 may be important for treating active disease, whereas stable disease may be treated by blocking CXCL10 alone (Rashighi et al , 2014; Regazzetti et al , 2015; Wang et al , 2016). Future clinical studies will need to be conducted to determine the therapeutic potential for targeting CXCR3 ligand expression in keratinocytes as a treatment for vitiligo.…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease

Richmond

Bangari²,

Essien

et al. 2017

Journal of Investigative Dermatology

151

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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.

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Section: Discussionmentioning

confidence: 99%

Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease

Richmond

Bangari²,

Essien

et al. 2017

Journal of Investigative Dermatology

151

View full text Add to dashboard Cite

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“…Chemokines are small, secreted proteins that act as chemoattractants to guide T cell migration. IFN-γ and IFN-γ-induced chemokines (CXCL9 and CXCL10) are highly expressed in the skin and blood of patients with vitiligo, as well as a mouse model (34–36). In addition, IFN-γ and CXCL10 are required for both disease progression and maintenance in a mouse model of the disease (34, 37).…”

Section: Vitiligo Pathogenesismentioning

confidence: 99%

Vitiligo Pathogenesis and Emerging Treatments

Rashighi

Harris

2017

Dermatologic Clinics

175

141

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The pathogenesis of vitiligo involves interplay between intrinsic and extrinsic melanocyte defects, innate immune inflammation, and T-cell-mediated melanocyte destruction. The goal of treatment is to not only halt disease progression but also promote repigmentation through melanocyte regeneration, proliferation, and migration. Treatment strategies that address all aspects of disease pathogenesis and repigmentation are likely to have greatest efficacy, a strategy that may require combination therapies. Current treatments generally involve nontargeted suppression of autoimmunity, whereas emerging treatments are likely to use a more targeted approach based on in-depth understanding of disease pathogenesis, which may provide higher efficacy with a good safety profile

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“…The importance of this pathway has been supported by translational studies of other groups (48-50) and by clinical studies in which the drugs that target this signaling axis were tested as treatments of vitiligo patients (51,52). Wang and colleagues tracked the levels of serum CXCL9 and CXCL10 in a cohort of patients and found that CXCL10 correlated with disease severity and inversely with treatment response (50), underpinning its role in human disease pathogenesis.…”

Section: Cd8+ T Cells Play a Central Role In Depigmentation: Killing mentioning

confidence: 99%

“…Wang and colleagues tracked the levels of serum CXCL9 and CXCL10 in a cohort of patients and found that CXCL10 correlated with disease severity and inversely with treatment response (50), underpinning its role in human disease pathogenesis. Inhibitors of JAK/STAT signaling, tofacitinib and ruxolitinib, have shown promising results in the repigmentation of two patients with vitiligo (51,52), further validating the importance of this signaling pathway in vitiligo pathogenesis.…”

Section: Cd8+ T Cells Play a Central Role In Depigmentation: Killing mentioning

confidence: 99%

Understanding mechanisms of autoimmunity through translational research in vitiligo

Strassner

Harris

2016

Current Opinion in Immunology

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Vitiligo is an autoimmune disease of the skin that leads to life-altering depigmentation and remains difficult to treat. However, clinical observations and translational studies over 30-40 years have led to the development of an insightful working model of disease pathogenesis: Genetic risk spanning both immune and melanocyte functions is pushed over a threshold by known and suspected environmental factors to initiate autoimmune T cell-mediated killing of melanocytes. While under cellular stress, melanocytes appear to signal innate immunity to activate T cells. Once the autoimmune T cell response is established, the IFN-γ-STAT1-CXCL10 signaling axis becomes the primary inflammatory pathway driving both progression and maintenance of vitiligo. This pathway is a tempting target for both existing and developing pharmaceuticals, but further detailing how melanocytes signal their own demise may also lead to new therapeutic targets. Research in vitiligo may be the future key to understand the pathogenesis of organ-specific autoimmunity, as vitiligo is common, reversible, progresses over the life of the individual, has been relatively well-defined, and is quite easy to study using translational and clinical approaches. What is revealed in these studies can lead to innovative treatments and also help elucidate the principles that underlie similar organ-specific autoimmune diseases, especially in cases where the target organ is less accessible.

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Increased expression of CXCR 3 and its ligands in patients with vitiligo and CXCL 10 as a potential clinical marker for vitiligo

Abstract: The CXCL10/CXCR3 axis mediates T-cell recruitment into the skin in progressive vitiligo. Blocking this chemotactic mechanism may present a new form of therapy. Serum CXCL10 may be a novel biomarker in monitoring disease activity and guiding treatment of progressive vitiligo.

Cited by 141 publications

References 46 publications

Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease

Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease

Vitiligo Pathogenesis and Emerging Treatments

Understanding mechanisms of autoimmunity through translational research in vitiligo

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