Molecular immunology · 2026
Promoting keratinocyte psoriasiform changes and IL-17RE expression: Potential role of GLT1D1 in linear psoriasis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Cheng Yufan, Chen Ling, Lin Jieyu, Peng Lu, Xiong Hao, Liu Guangren, Shen Zhu
Аннотация
BACKGROUND: Linear psoriasis is a rare variant of psoriasis characterized by erythema and scaling along the Blaschko lines. Its pathogenesis remains unknown.
OBJECTIVE: To investigate the molecular and immunological mechanisms of linear psoriasis through gene mutation analysis and in vitro experiments and identify potential combined therapeutic targets for psoriasis.
METHODS: Whole-exome sequencing was performed on linear lesion, clinically normal skin, and peripheral blood from linear psoriasis patient to identify somatic mutations. Candidate gene expression was assessed using public RNA-seq data of linear and classic psoriasis vulgaris, dataset before and after IL-17 antagonist Brodalumab treatment, and single-cell data of recurrent psoriasis lesions. Immunofluorescence staining confirmed gene expression and distribution. In vitro keratinocyte assays evaluated effects on proliferation and inflammation. Based on these findings, the patient received IL-17 antagonist therapy (Ixekizumab).
RESULTS: An increased copy number variant of Glycosyltransferase 1 Domain Containing 1 (GLT1D1), not previously reported, was identified in the epidermis of linear psoriasis. GLT1D1 was highly expressed in both linear psoriasis and classic psoriasis vulgaris, as well as in recurrent lesions and in patients who failed to achieve PASI75 with IL-17 antagonist therapy. In keratinocytes, GLT1D1 overexpression promoted cell proliferation, enhanced proinflammatory cytokine secretion, and activated IL-17 signaling, particularly via IL-17RE upregulation. In imiquimod-induced mouse models, GLT1D1 overexpression aggravated psoriasiform inflammation. Clinical improvement was observed in the patient after treatment with ixekizumab.
CONCLUSION: GLT1D1, with an abnormally high copy number, may contribute to psoriasiform changes in keratinocytes by promoting proliferation, increasing proinflammatory cytokine secretion, and enhancing IL-17RE expression.
OBJECTIVE: To investigate the molecular and immunological mechanisms of linear psoriasis through gene mutation analysis and in vitro experiments and identify potential combined therapeutic targets for psoriasis.
METHODS: Whole-exome sequencing was performed on linear lesion, clinically normal skin, and peripheral blood from linear psoriasis patient to identify somatic mutations. Candidate gene expression was assessed using public RNA-seq data of linear and classic psoriasis vulgaris, dataset before and after IL-17 antagonist Brodalumab treatment, and single-cell data of recurrent psoriasis lesions. Immunofluorescence staining confirmed gene expression and distribution. In vitro keratinocyte assays evaluated effects on proliferation and inflammation. Based on these findings, the patient received IL-17 antagonist therapy (Ixekizumab).
RESULTS: An increased copy number variant of Glycosyltransferase 1 Domain Containing 1 (GLT1D1), not previously reported, was identified in the epidermis of linear psoriasis. GLT1D1 was highly expressed in both linear psoriasis and classic psoriasis vulgaris, as well as in recurrent lesions and in patients who failed to achieve PASI75 with IL-17 antagonist therapy. In keratinocytes, GLT1D1 overexpression promoted cell proliferation, enhanced proinflammatory cytokine secretion, and activated IL-17 signaling, particularly via IL-17RE upregulation. In imiquimod-induced mouse models, GLT1D1 overexpression aggravated psoriasiform inflammation. Clinical improvement was observed in the patient after treatment with ixekizumab.
CONCLUSION: GLT1D1, with an abnormally high copy number, may contribute to psoriasiform changes in keratinocytes by promoting proliferation, increasing proinflammatory cytokine secretion, and enhancing IL-17RE expression.