Zhang Deyu, Ma Congjia, Wang Zhen, Liu Yanfang, Liu Zaoqu, Li Wanshun, Liu Yue, Wu Chang, Sun Liqi, Jiang Fei, Jiang Hui, Su Xiaoju, Peng Lisi, Li Jiayu, Wang Xinyue, Yin Hua, Wan Dongling, Zhou Yuyan, Tian Xiaorong, Li Shiyu, Jin Zhendong, Ji Baoan, Li Zhaoshen, Huang Haojie
Department of Gastroenterology, Changhai Hospital, Shanghai, 200433, China.
National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Adv Sci (Weinh). 2025 Mar;12(12):e2412282. doi: 10.1002/advs.202412282. Epub 2025 Jan 31.
Autoimmune pancreatitis (AIP) is identified as a severe chronic immune-related disorder in pancreas, including two subtypes. In this study, pancreatic lesions in patients diagnosed as either type 1 AIP or type 2 AIP are examined, and these patients' peripheral blood at single-cell level. Furthermore, flow cytometry, immunofluorescence, and functional assays are performed to verify the identified cell subtypes. In type 1 AIP, there is a notable increase in the amount of B cells and plasma cells, and IgG4+ plasma cells are key pathogenic cells of AIP. The differentiation path of naïve-stage B cells into IgG4+ produced plasma cells is observed, and an increased amount of T helper cells and T follicular helper (Tfh) cells. This study also reveals that HIF-1α, an activated transcriptional factor, can directly bind to promoter site of NAMPT, promoting higher levels of visfatin production in HIF1A+ classical monocytes. Pancreatic stellate cells can be activated by extracellular visfatin and promote the development of fibrotic response in pancreatic lesions across both AIP subtypes. The current findings shed light on the exploration of dynamic alterations in peripheral blood cells and cell subgroups in pancreatic lesions of AIP, while elucidating a pathogenic cell subset and potential fibrosis mechanism of AIP.
自身免疫性胰腺炎（AIP）被认为是一种严重的胰腺慢性免疫相关疾病，包括两种亚型。在本研究中，对诊断为1型AIP或2型AIP的患者的胰腺病变以及这些患者单细胞水平的外周血进行了检查。此外，还进行了流式细胞术、免疫荧光和功能测定，以验证所鉴定的细胞亚型。在1型AIP中，B细胞和浆细胞数量显著增加，IgG4 +浆细胞是AIP的关键致病细胞。观察到初始阶段B细胞向产生IgG4 +的浆细胞的分化途径，以及辅助性T细胞和滤泡辅助性T（Tfh）细胞数量增加。本研究还表明，活化的转录因子HIF-1α可直接结合烟酰胺磷酸核糖转移酶（NAMPT）的启动子位点，促进HIF1A +经典单核细胞中更高水平的内脂素产生。胰腺星状细胞可被细胞外内脂素激活，并促进两种AIP亚型胰腺病变中纤维化反应的发展。目前的研究结果为探索AIP胰腺病变中外周血细胞和细胞亚群的动态变化提供了线索，同时阐明了AIP的致病细胞亚群和潜在的纤维化机制。
