Dectin-1 is a well-characterized C-type lectin receptor involved in anti-fungal immunity through the recognition of polysaccharides; however, molecular mechanisms and outcomes initiated through self-recognition have not been fully understood. Here, we purified a water-soluble fraction from mouse liver that acts as a Dectin-1 agonist. To address the physiological relevance of this recognition, we utilized sterile liver inflammation models. The CCl₄-induced hepatitis model showed that Dectin-1 deficiency led to reduced inflammation through decreased inflammatory cell infiltration and lower pro-inflammatory cytokine levels. Moreover, in a NASH model induced by streptozotocin and a high-fat diet, hepatic inflammation and fibrosis were ameliorated in Dectin-1-deficient mice. The Dectin-1 agonist activity was increased in the water-soluble fraction from NASH mice, suggesting a potential pathogenic cycle between Dectin-1 activation and hepatitis progression. In vivo administration of the fraction into mice induced hepatic inflammation. These results highlight a role of self-recognition through Dectin-1 that triggers hepatic innate immune responses and contributes to the exacerbation of inflammation in pathogenic settings. Thus, the blockade of this axis may provide a therapeutic option for liver inflammatory diseases.

中文翻译：

---

通过 Dectin-1 进行自我识别会加剧肝脏炎症

Dectin-1 是一种特征明确的 C 型凝集素受体，通过识别多糖参与抗真菌免疫；然而，通过自我认知引发的分子机制和结果尚未完全了解。在这里，我们从小鼠肝脏中纯化了一种水溶性组分，作为 Dectin-1 激动剂。为了解决这种认识的生理相关性，我们利用了无菌肝脏炎症模型。 CCl ₄诱导的肝炎模型表明，Dectin-1 缺乏可通过减少炎症细胞浸润和降低促炎细胞因子水平来减轻炎症。此外，在链脲佐菌素和高脂肪饮食诱导的 NASH 模型中，Dectin-1 缺陷小鼠的肝脏炎症和纤维化得到改善。 NASH 小鼠的水溶性部分中的 Dectin-1 激动剂活性增加，表明 Dectin-1 激活和肝炎进展之间存在潜在的致病循环。在小鼠体内将该级分施用诱导肝脏炎症。这些结果强调了 Dectin-1 自我识别的作用，它触发肝脏先天免疫反应，并导致致病环境中炎症的加剧。因此，阻断该轴可能为肝脏炎症性疾病提供一种治疗选择。