Immunohistochemistry Revealed Distinct IL-36γ Localization Among Different Skin Diseases

IL-36γ is highly expressed in psoriatic skin lesions and promotes neutrophil infiltration through the induction of neutrophil chemotactic chemokines. While IL-36γ has been established to play an important role in the pathogenesis of psoriasis, its localization in the psoriatic epidermis has not been fully elucidated, and the difference in its expression patterns among other inflammatory skin diseases remains unclear. We investigated IL-36γ localization using immunohistochemistry in skin specimens from patients with psoriasis vulgaris (n = 36), generalized pustular psoriasis (n = 11), pyoderma gangrenosum (n = 6), palmoplantar pustulosis (n = 6), tumor necrosis factor inhibitor-induced paradoxical reaction (n = 3), pustular drug eruption (n = 5), atopic dermatitis (n = 11), tinea infection (n = 3), and mycosis fungoides (n = 9), as well as uninvolved skin adjacent to benign tumors (n = 4). Staining scores were assessed based on intensity and distribution, and nuclear positivity was compared among diseases. IL-36γ was strongly expressed in the upper epidermis of psoriasis vulgaris and generalized pustular psoriasis, with staining scores significantly higher than those in atopic dermatitis and adjacent normal skin. Expression in pyoderma gangrenosum, palmoplantar pustulosis, paradoxical reaction, and pustular drug eruption was comparable to psoriasis vulgaris. Nuclear staining of IL-36γ was frequent in psoriasis vulgaris (33/36, 92%) and generalized pustular psoriasis (11/11, 100%), but absent in pyoderma gangrenosum. The difference in nuclear positivity between psoriasis and pyoderma gangrenosum was statistically significant. These findings confirm that IL-36γ is highly expressed in psoriatic lesions but is not specific to psoriasis, as it is also upregulated in other inflammatory skin diseases. Nuclear staining was observed in psoriasis but not in pyoderma gangrenosum, suggesting a potential disease-specific localization pattern. The biological significance and mechanism of nuclear localization remain unclear, as the IL-36γ molecule lacks a nuclear localization signal. Our findings highlight that the localization of IL-36γ differs among inflammatory skin diseases, suggesting that it may reflect pathogenic differences and warrant further investigation.