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Abstract：
Psoriasis is a common chronic inflammatory skin disease that significantly impacts the patients\' quality of life. Recent studies highlighted the function of the interleukin (IL)-1 family member IL-38 in skin homeostasis and suggested an anti-inflammatory role for this cytokine in psoriasis. In this study, we generated mice specifically overexpressing the IL-38 protein in epidermal keratinocytes. We confirmed IL-38 overexpression in the skin by Western blotting. We further detected the protein by ELISA in the plasma, as well as in conditioned media of skin explants isolated from IL-38 overexpressing mice, indicating that IL-38 produced in the epidermis is released from keratinocytes and can be found in the circulation. Unexpectedly, epidermal IL-38 overexpression did not impact the global severity of imiquimod (IMQ)-induced skin inflammation, Similarly, keratinocyte activation and differentiation in IMQ-treated skin were not affected by increased IL-38 expression and there was no global effect on local or systemic inflammatory responses. Nevertheless, we observed a selective inhibition of CXCL1 and IL-6 production in response to IMQ in IL-38 overexpressing skin, as well as reduced Ly6g mRNA levels, suggesting decreased neutrophil infiltration. Epidermal IL-38 overexpression also selectively affected the desquamation process during IMQ-induced psoriasis, as illustrated by reduced plaque formation. Taken together, our results validate the generation of a new mouse line allowing for tissue-specific IL-38 overexpression. Interestingly, epidermal IL-38 overexpression selectively affected specific disease-associated readouts during IMQ-induced psoriasis, suggesting a more complex role of IL-38 in the inflamed skin than previously recognized. In particular, our data highlight a potential involvement of IL-38 in the regulation of skin desquamation.
摘要：
银屑病是一种常见的慢性炎症性皮肤病，严重影响患者的生活质量。最近的研究强调了白细胞介素（IL）-1家族成员IL-38在皮肤稳态中的功能，并暗示了这种细胞因子在牛皮癣中的抗炎作用。在这项研究中,我们产生了在表皮角质形成细胞中特异性过表达IL-38蛋白的小鼠。我们通过Western印迹证实了皮肤中IL-38的过表达。我们进一步通过ELISA检测血浆中的蛋白质，以及在从IL-38过表达小鼠中分离出的皮肤外植体的条件培养基中，这表明在表皮中产生的IL-38从角质形成细胞释放并且可以在循环中发现。出乎意料的是,表皮IL-38过表达不影响咪喹莫特（IMQ）诱导的皮肤炎症的整体严重程度，同样，在IMQ处理的皮肤中角质形成细胞的活化和分化不受IL-38表达增加的影响,并且对局部或全身炎症反应没有整体影响.然而，我们观察到在IL-38过表达的皮肤中响应IMQ的CXCL1和IL-6产生的选择性抑制，以及降低Ly6gmRNA水平，提示中性粒细胞浸润减少。表皮IL-38过表达也选择性影响IMQ诱导的银屑病脱皮过程，如斑块形成减少所示。一起来看,我们的结果验证了一个允许组织特异性IL-38过表达的新小鼠细胞系的产生.有趣的是,表皮IL-38过表达选择性地影响IMQ诱导的银屑病期间的特定疾病相关读数，这表明IL-38在发炎的皮肤中的作用比以前认识到的更复杂。特别是,我们的数据强调了IL-38可能参与皮肤脱屑的调节.
