Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
J Invest Dermatol. 2022 Feb;142(2):402-413. doi: 10.1016/j.jid.2021.06.030. Epub 2021 Jul 30.
Dermal fibroblasts are strategically positioned underneath the basal epidermis layer to support keratinocyte proliferation and extracellular matrix production. In inflammatory conditions, these fibroblasts produce cytokines and chemokines that promote the chemoattraction of immune cells into the dermis and the hyperplasia of the epidermis, two characteristic hallmarks of psoriasis. However, how dermal fibroblasts specifically contribute to psoriasis development remains largely uncharacterized. In this study, we investigated through which cytokines and signaling pathways dermal fibroblasts contribute to the inflammatory features of psoriatic skin. We show that dermal fibroblasts from lesional psoriatic skin are important producers of inflammatory mediators, including IL-6, CXCL8, and CXCL2. This increased cytokine production was found to be regulated by ZFP36 family members ZFP36, ZFP36L1, and ZFP36L2, RNA-binding proteins with mRNA-degrading properties. In addition, the expression of ZFP36 family proteins was found to be reduced in chronic inflammatory conditions that mimic psoriatic lesional skin. Collectively, these results indicate that dermal fibroblasts are important producers of cytokines in psoriatic skin and that reduced expression of ZFP36 members in psoriasis dermal fibroblasts contributes to their inflammatory phenotype.
皮肤成纤维细胞位于基底层表皮层下方，以支持角质形成细胞的增殖和细胞外基质的产生。在炎症条件下，这些成纤维细胞产生细胞因子和趋化因子，促进免疫细胞向真皮的趋化和表皮的增生，这是银屑病的两个特征性标志。然而，皮肤成纤维细胞如何特异性地促进银屑病的发展在很大程度上仍未被描述。在这项研究中，我们通过研究皮肤成纤维细胞通过哪些细胞因子和信号通路促进银屑病皮肤的炎症特征来进行调查。我们表明，来自病变银屑病皮肤的皮肤成纤维细胞是炎症介质的重要产生者，包括 IL-6、CXCL8 和 CXCL2。这种增加的细胞因子产生被发现受到 ZFP36 家族成员 ZFP36、ZFP36L1 和 ZFP36L2 的调节，ZFP36 家族是具有 mRNA 降解特性的 RNA 结合蛋白。此外，在模拟银屑病病变皮肤的慢性炎症条件下，ZFP36 家族蛋白的表达被发现减少。总的来说，这些结果表明皮肤成纤维细胞是银屑病皮肤中细胞因子的重要产生者，并且银屑病皮肤成纤维细胞中 ZFP36 成员的表达减少导致其炎症表型。
