High-fat diet aggravates experimental autoimmune pancreatitis through the activation of type I interferon signaling pathways
High-fat diet aggravates experimental autoimmune pancreatitis through the activation of type I interferon signaling pathways
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高脂饮食通过激活I型干扰素信号通路加重实验性自身免疫性胰腺炎
DOI：
10.1016/j.bbrc.2022.11.030
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发表时间：
2022
影响因子：
3.1
通讯作者：
Watanabe Tomohiro
中科院分区：
文献类型：
--
作者：
Sekai Ikue;Minaga Kosuke;Hara Akane;Otsuka Yasuo;Kurimoto Masayuki;Omaru Naoya;Okai Natsuki;Masuta Yasuhiro;Takada Ryutaro;Yoshikawa Tomoe;Kamata Ken;Kudo Masatoshi;Watanabe Tomohiro
自身免疫性胰腺炎（AIP）是胰腺的自身免疫性疾病，其特征在于增强的IgG4抗体应答和多器官受累。AIP是全身性IgG4相关疾病（IgG4-RD）的胰腺表现。虽然AIP和IgG4-RD主要发生在中年和老年男性中，但对饮食习惯和生活方式在这些疾病发病机制中的作用知之甚少。在这项研究中，我们研究了中年和老年男性偏好的高脂肪饮食（HFD）是否会增加对实验性AIP的敏感性。我们通过重复注射聚肌胞苷酸在MRL/MpJ小鼠中建立AIP模型。HFD可加重AIP的发展，并促进产生干扰素（IFN）-α的浆细胞样树突状细胞（pDC）在胰腺的积聚。然而，HFD不会增加自身免疫性涎腺炎的严重程度，这是另一种与AIP和IgG4-RD相关的疾病。I型IFN信号通路的中和防止了HFD诱导的严重AIP的发展。相比之下，肠漏不太可能与HFD诱导的AIP恶化相关，这一点可以通过空肠或回肠紧密连接蛋白表达缺乏显著改变来证明。这些数据表明，HFD通过活化产生IFN-α的pDC而加剧实验性AIP。
Autoimmune pancreatitis (AIP) is an autoimmune disorder of the pancreas characterized by enhanced IgG4 antibody responses and multiple organ involvement. AIP is a pancreatic manifestation of the systemic IgG4-related disease (IgG4-RD). Although AIP and IgG4-RD predominantly occur in middle-aged and elderly men, the roles of eating habits and lifestyle in the pathogenesis of these conditions are poorly understood. In this study, we examined whether a high-fat diet (HFD), preferred by middle-aged and elderly men, increases sensitivity to experimental AIP. We modeled AIP in MRL/MpJ mice by repeated injections of polyinosinic:polycytidylic acid. HFD exacerbated AIP development and promoted pancreatic accumulation of interferon (IFN)-α-producing plasmacytoid dendritic cells (pDCs). However, HFD did not increase the severity of autoimmune sialadenitis, another disorder associated with AIP and IgG4-RD. Neutralization of type I IFN signaling pathways prevented the development of severe AIP induced by HFD. In contrast, leaky gut was less likely to be associated with the HFD-induced exacerbation of AIP, as was evidenced by the lack of significant alterations in the jejunal or ileal expression of tight junction proteins. These data suggest that HFD exacerbates experimental AIP through the activation of pDCs producing IFN-α.