Seok SH, et al. Allergy Asthma Immunol Res. 2020 Nov;12(6):1063-1065. https://doi.org/10.4168/aair.2020.12.6.1063

Seok SH, et al. Ann Dermatol. 2023 May;35:e63. https://doi.org/10.5021/ad.21.067

The activation of signal transducer and activator of transcription 3 (STAT3), as well as up-regulation of cytokines and growth factors to promote STAT3 activation, have been found in the epidermis of psoriatic lesions. Recently, a series of synthetic compounds possessing the Michael acceptor have been reported as STAT3 inhibitors by covalently binding to cysteine of STAT3. We synthesized a Michael acceptor analog, SKSI-0412, and confirmed the binding affinity between STAT3 and SKSI-0412. We hypothesized that the SKSI-0412 can inhibit interleukin (IL)-17A-induced inflammation in keratinocytes. The introduction of IL-17A increased the phosphorylation of STAT3 in keratinocytes, whereas the inactivation of STAT3 by SKSI-0412 reduced IL-17A-induced STAT3 phosphorylation and IκBζ expression. In addition, human β defensin-2 and S100A7, which are regulated by IκBζ, were significantly decreased with SKSI-0412 administration. We also confirmed that SKSI-0412 regulates cell proliferation, which is the major phenotype of psoriasis. Based on these results, we suggest targeting STAT3 with SKSI-0412 as a novel therapeutic strategy to regulate IL-17A-induced psoriatic inflammation in keratinocytes.

Seok SH, et al. Ann Dermatol. 2023 May;35:e68. https://doi.org/10.5021/ad.21a.064

Vitiligo is an autoimmune disease in which CD8+ T-cells target and destroy melanocytes, leaving areas of skin without pigment production. Nonsegmental vitiligo, the classical form of the disease, results in symmetrical, bilateral white patches. Vitiligo is a chronic, unpredictable disease, characterized by flares, with depigmentation and periods of disease arrest alternating. This process can be stressful and negatively impact one’s quality of life. Various hypotheses have been offered, including cellular stress causing degeneration of melanocytes, chemical toxicity causing melanocyte death, and neural changes that influence melanocytes or their ability to produce melanin. Recently, the interaction between oxidative stress and autoimmune-mediated melanocyte loss has been proposed as the primary pathogenesis of vitiligo. It is now well accepted that interferon-γ and/or C-X-C motif chemokine ligand 10 axis is functionally required for both progression and maintenance of vitiligo, making this pathway a potential therapeutic target. Most therapeutic interventions in the management of vitiligo have been developed based on this immunopathogenesis. This article aims to review the current understanding of the vitiligo pathogenesis.