Alterations in extracellular matrix (ECM) components that modulate inflammatory cell behavior have been shown to serve as early starters for multifactorial diseases such as fibrosis and cancer. Here, we demonstrated that loss of the ECM glycoprotein EMILIN-1 alters the inflammatory context in skin during IMQ-induced psoriasis, a disease characterized by a prominent inflammatory infiltrate and alteration of vessels that appear dilated and tortuous. Abrogation of EMILIN-1 expression or expression of the EMILIN-1 mutant E933A impairs macrophage polarization and leads to imbalanced tissue homeostasis. We found that EMILIN-1 deficiency is associated with dilated lymphatic vessels, increased macrophage recruitment and psoriasis severity. Importantly, the null or mutant EMILIN-1 background was characterized by the induction of a myofibroblast phenotype, which in turn drove macrophages towards the M1 phenotype. By using the transgenic mouse model carrying the E933A mutation in the gC1q domain of EMILIN-1, which abolishes the interaction with α4- and α9-integrins, we demonstrated that the observed changes in TGFβ signaling were due to both the EMI and gC1q domains of EMILIN-1. gC1q may exert multiple functions in psoriasis, in the context of a final, more consistent inflammatory condition by controlling skin homeostasis via interaction with both keratinocytes and fibroblasts, influencing non-canonical TGFβ signaling, and likely acting on lymphatic vessel structure and function. The analyses of human psoriatic lesions, in which lower levels of EMILIN-1 were present with a very rare association with lymphatic vessels, support the multifaceted role of this ECM component in the skin inflammatory scenario.

调节炎症细胞行为的细胞外基质 (ECM) 成分的改变已被证明可作为多因素疾病（如纤维化和癌症）的早期起始物。在这里，我们证明了 ECM 糖蛋白 EMILIN-1 的缺失会改变 IMQ 诱导的银屑病期间皮肤的炎症环境，这种疾病的特征是显着的炎症浸润和血管扩张和曲折的改变。消除 EMILIN-1 表达或 EMILIN-1 突变体 E933A 的表达会损害巨噬细胞极化并导致组织稳态失衡。我们发现 EMILIN-1 缺乏与淋巴管扩张、巨噬细胞募集增加和银屑病严重程度有关。重要的是，无效或突变的 EMILIN-1 背景的特征是诱导肌成纤维细胞表型，这反过来又将巨噬细胞推向 M1 表型。通过使用在 EMILIN-1 的 gC1q 结构域中携带 E933A 突变的转基因小鼠模型，它消除了与 α4-和 α9-整合素的相互作用，我们证明观察到的 TGFβ 信号变化是由于 EMI 和 gC1q 结构域引起的。艾米林-1。gC1q 可能在银屑病中发挥多种功能，在最终的、更一致的炎症状态下，通过与角质形成细胞和成纤维细胞相互作用来控制皮肤稳态，影响非经典 TGFβ 信号传导，并可能作用于淋巴管结构和功能。对人类银屑病病变的分析，其中 EMILIN-1 水平较低，与淋巴管的关联非常罕见，