Role of Cytokines in Vitiligo: Pathogenesis and Possible Targets for Old and New Treatments

Custurone, Paolo; Bartolomeo, Luca Di; Irrera, Natasha; Borgia, Francesco; Altavilla, Domenica; Bitto, Alessandra; Pallio, Giovanni; Squadrito, Francesco; Vaccaro, Mario

doi:10.3390/ijms222111429

Cited by 27 publications

(24 citation statements)

References 113 publications

(153 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The inflammatory signaling in vitiligo foresees the activation of epidermal dendritic and natural killer (NK) cells, which release IFN- and stimulate keratinocytes to produce chemokines, which, in turn, enlist and activate cytotoxic CD8 + T cells. The increased expression of inflammatory mediators including IFN-, tumor necrosis factor-, IL-6, and IL-1 cytokines, as well as the chemokines CXCL9, CXCL10, and CXCL16 has been widely reported in lesional and perilesional skin (48,(63)(64)(65). Several studies attempted to define some of these messengers as possible reliable biomarkers of disease activity and severity, both at serum and tissue levels (21,64,65).…”

Section: Discussionmentioning

confidence: 99%

Altered epidermal proliferation, differentiation, and lipid composition: Novel key elements in the vitiligo puzzle

et al. 2022

View full text Add to dashboard Cite

Vitiligo is an acquired skin depigmentation disease involving multiple pathogenetic mechanisms, which ultimately direct cytotoxic CD8 + cells to destroy melanocytes. Abnormalities have been described in several cells even in pigmented skin as an expression of a functional inherited defect. Keratinocytes regulate skin homeostasis by the assembly of a proper skin barrier and releasing and responding to cytokines and growth factors. Alterations in epidermal proliferation, differentiation, and lipid composition as triggers for immune response activation in vitiligo have not yet been investigated. By applying cellular and lipidomic approaches, we revealed a deregulated keratinocyte differentiation with altered lipid composition, associated with impaired energy metabolism and increased glycolytic enzyme expression. Vitiligo keratinocytes secreted inflammatory mediators, which further increased following mild mechanical stress, thus evidencing immune activation. These findings identify intrinsic alterations of the nonlesional epidermis, which can be the prime instigator of the local inflammatory milieu that stimulates immune responses targeting melanocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Altered epidermal proliferation, differentiation, and lipid composition: Novel key elements in the vitiligo puzzle

et al. 2022

View full text Add to dashboard Cite

show abstract

“…[5][6][7][8] Activated melanocyte-specific skin CXCR3 + CD8 + T-cells produce high levels of interferon gamma (INF-γ) and tumor necrosis factor alpha (TNF-α), which promote the detachment and apoptosis of MCs through E-cadherin disruption partly caused by increased matrix metalloproteinases 9 (MMP-9) produced by keratinocytes. 9,10 Inhibition of MMP-9 or the IFN-γ signaling pathway mediated by the Janus kinasesignal transducer and activator of transcription (JAK-STAT) prevents MCs detaching from the basal layer in vitro and in vivo. 10 Studies showed that JAK inhibitors target the JAK/STAT signaling pathway and are now approved to treat many immune diseases.…”

Section: Introductionmentioning

confidence: 99%

Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro

Dong

Huang

et al. 2022

Dose-Response

View full text Add to dashboard Cite

Objective To evaluate the clinical efficacy and safety of baricitinib, a Janus kinase (JAK) inhibitor, in treating patient with progressing vitiligo, and to further explore the regulation of baricitinib on melanocytes (MCs) in vitro. Methods Four patients with progressing vitiligo were treated with oral baricitinib for a total of 12 weeks. MCs were cultured in vitro and irradiated by high-dose ultraviolet B (UVB, 150mJ/cm2) to make an MC damaged model (MC-Ds). Baricitinib was added at a final concentration of 25 μM. Dopamine staining and NaOH method were used to measure the tyrosinase activity and melanin level, respectively, real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure the mRNA levels of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1). Results Significant re-pigmentation was observed in the week 12 without obvious side effects. Depigmentation occurred in 2 patients at the 3-month follow-up. Laboratory research found that higher doses of UVB irradiation (150mJ/cm2) could decrease melanin content of MCs, baricitinib (25 μM) could significantly promote tyrosinase activity, melanin content, and TYR, TRP-1 gene expression of MC-Ds. Conclusion Our preliminary study showed that baricitinib was effective and safe in treating progressing vitiligo. Baricitinib could promote tyrosinase activity, melanin content and TYR, TRP1 gene expression of MC-Ds in vitro.

show abstract

“…Vitiligo is a common progressive depigmentation of the skin due to selective destruction of melanocytes ( Vaccaro et al, 2015 ; Vaccaro et al, 2017a ). Although the pathogenesis remains scarcely known, it seems to be related to genetic predisposing factors, oxidative stress and autoimmune dysregulation ( Vaccaro et al, 2016 ; Vaccaro et al, 2017b ; Custurone et al, 2021 ). PDT is proven to inhibit melanogenesis in vitro , reducing melanocytes melanin content and tyrosinase activity.…”

Section: Miscellaneamentioning

confidence: 99%

Photodynamic therapy in pediatric age: Current applications and future trends

et al. 2022

Self Cite

View full text Add to dashboard Cite

Photodynamic therapy (PDT) is a photochemotherapy based on local application of a photosensitive compound and subsequent exposure to a light source of adequate wavelength. It is a non-invasive therapeutic procedure widely used in oncodermatology for treatment of numerous skin cancers, but in the last years its use has been gradually extended to an increasing list of skin diseases of both infectious and inflammatory nature. Although PDT is proven as a safe and effective therapeutic option in adults, its use is not well standardized in the pediatric population. In this review, we will focus on clinical applications, mechanisms of action, protocols, and adverse events in children and adolescents. Most of pediatric experiences concerned treatment of skin cancers in Gorlin syndrome and xeroderma pigmentosum, acne vulgaris, and viral warts, but other applications emerged, such as cutaneous lymphoma and pseudo-lymphomas, necrobiosis lipoidica, hidradenitis suppurativa, dissecting cellulitis, leishmaniasis, angiofibromas, verrucous epidermal nevus, and linear porokeratosis. In these pediatric diseases, PDT appeared as an effective therapeutic alternative. The results on vitiligo were limited and not fully encouraging. Although highly versatile, PDT is not a therapy for all skin diseases, and a deeper knowledge of its mechanisms of action is required to better define its spectrum of action and safety in pediatric patients.

show abstract

Role of Cytokines in Vitiligo: Pathogenesis and Possible Targets for Old and New Treatments

Cited by 27 publications

References 113 publications

Altered epidermal proliferation, differentiation, and lipid composition: Novel key elements in the vitiligo puzzle

Altered epidermal proliferation, differentiation, and lipid composition: Novel key elements in the vitiligo puzzle

Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro

Photodynamic therapy in pediatric age: Current applications and future trends

Contact Info

Product

Resources

About