Interleukin‐38 (IL‐38) is strongly associated with chronic inflammatory diseases; however, its role in tumorigenesis is poorly understood. We demonstrated that expression of IL‐38, which exhibits high expression in the skin, is downregulated in human cutaneous squamous cell carcinoma and 7,12‐dimethylbenzanthracene/12‐O‐tetradecanoyl phorbol‐13‐acetate‐induced mouse skin tumorigenesis. IL‐38 keratinocyte‐specific knockout mice displayed suppressed skin tumor formation and malignant progression. Keratinocyte‐specific deletion of IL‐38 was associated with reduced expression of inflammatory cytokines, leading to reduced myeloid cell infiltration into the local tumor microenvironment. IL‐38 is dispensable for epidermal mutagenesis, but IL‐38 keratinocyte‐specific deletion reduces proliferative gene expression along with epidermal cell proliferation and hyperplasia. Mechanistically, we first demonstrated that IL‐38 activates the c‐Jun N‐terminal kinase (JNK)/activator protein 1 signal transduction pathway to promote the expression of cancer‐related inflammatory cytokines and proliferation and migration of tumor cells in an IL‐1 receptor‐related protein 2 (IL‐1Rrp2)‐dependent manner. Our findings highlight the role of IL‐38 in the regulation of epidermal cell hyperplasia and pro‐tumorigenic microenvironment through IL‐1Rrp2/JNK and suggest IL‐38/IL‐1Rrp2 as a preventive and potential therapeutic target in skin cancer.

Linear IgA/IgG bullous dermatosis (LAGBD) is a rare autoimmune subepidermal bullous disorder characterized by linear deposition of concurrent IgA and IgG autoantibodies along the basement membrane zone (BMZ). The clinical features of LAGBD can be diverse, including tense blisters, erosions, erythema, crusting and mucosa involvement, while papules or nodules are generally absent. In this study, we present a unique case of LAGBD, which showed prurigo nodularis-like clinical appearance on physical examination, linear deposition of IgG and C3 along the basement membrane zone (BMZ) in direct immunofluorescence (DIF), IgA autoantibodies against the 97-kDa and 120-kDa of BP180 and IgG autoantibodies against the 97-kDa of BP180 by immunoblotting (IB), while BP180 NC16a domain, BP230, and laminin 332 were negative by enzyme-linked immunosorbent assay (ELISA). After administration of minocycline, the skin lesions improved. We performed a literature review of LAGBD cases with heterogeneous autoantibodies and found clinical presentations of most cases resemble bullous pemphigoid (BP) and linear IgA bullous disease (LABD), which is consistent with previous reported findings. We aim to increase our understanding of this disorder and to enhance the importance of applying immunoblot analyses and other serological detection tools in clinic for precise diagnosis as well as accurate treatment strategy of various autoimmune bullous dermatoses.