The IL-1 cytokine family includes eleven members, among which Il-36α, β and γ, IL-36Ra and IL-38. The IL-36 cytokines are involved in the pathogenesis of psoriasis. IL-38 is also expressed in the skin and was previously proposed to act as an IL-36 antagonist. In this study, we thus examined expression and function of Il-38 in a mouse model of imiquimod (IMQ)-induced skin inflammation. Il-38 mRNA was detected in the epidermis and in primary mouse keratinocytes, but not in dermal fibroblasts. At the peak of IMQ-induced inflammation, skin Il-38 mRNA levels were reduced, whereas Il-36ra mRNA expression increased. The severity of IMQ-induced skin inflammation, as assessed by recording ear thickness and histological changes, was similar in Il-38 KO and WT littermate control mice, while, in contrast, Il-36ra-deficient mice displayed more severe skin pathology than their WT littermates. Il-38-deficiency had no impact on IMQ-induced expression of proinflammatory mediators in the skin in vivo, on the basal expression of various cytokines or chemokines by cultured primary keratinocytes and dermal fibroblasts in vitro, or on the response of these cells to Il-36β. Finally, after cessation of topical IMQ application, the resolution of skin inflammation was also not altered in Il-38 KO mice. In conclusion, Il-38-deficiency did not impact the development or resolution of IMQ-induced skin inflammation. Our observations further suggest that endogenous Il-38 does not exert Il-36 inhibitory activity in this model, or in cultured skin cells. A potential anti-inflammatory function of Il-38 in mouse skin thus still remains to be demonstrated.

IL-1细胞因子家族包括11个成员，其中Il-36α，β和γ，IL-36Ra和IL-38。IL-36细胞因子参与牛皮癣的发病机理。IL-38也在皮肤中表达，并且先前被提议充当IL-36拮抗剂。在这项研究中，我们因此检查了咪喹莫特（IMQ）诱导的皮肤炎症小鼠模型中Il-38的表达和功能。在表皮和原代小鼠角质形成细胞中检测到Il-38 mRNA，但在真皮成纤维细胞中未检测到。在IMQ诱发的炎症高峰时，皮肤Il-38 mRNA水平降低，而Il-36ramRNA表达增加。通过记录耳厚和组织学变化评估，IMQ引起的皮肤炎症的严重程度在Il-38 KO和WT同窝幼仔对照小鼠中相似，而相比之下，Il-36ra缺陷小鼠表现出比其更严重的皮肤病理WT同窝幼仔。Il-38缺乏症对IMQ诱导的体内皮肤促炎性介质表达，体外培养的原代角质形成细胞和真皮成纤维细胞的各种细胞因子或趋化因子的基础表达没有影响或这些细胞对Il-36β的反应。最后，在停止局部IMQ应用后，II-38 KO小鼠中皮肤炎症的分辨率也没有改变。总之，II-38缺乏症并不影响IMQ引起的皮肤炎症的发展或消退。我们的观察结果进一步表明，内源性Il-38在该模型或培养的皮肤细胞中不发挥Il-36抑制活性。因此，II-38在小鼠皮肤中的潜在抗炎功能仍有待证明。