2. Academic Validation
  3. Unraveling the Microenvironment and the Pathogenic Axis of HIF-1α-Visfatin-Fibrosis in Autoimmune Pancreatitis Using a Single-Cell Atlas

Unraveling the Microenvironment and the Pathogenic Axis of HIF-1α-Visfatin-Fibrosis in Autoimmune Pancreatitis Using a Single-Cell Atlas

  • Adv Sci (Weinh). 2025 Jan 31:e2412282. doi: 10.1002/advs.202412282.
Deyu Zhang 1 2,  Congjia Ma 1 2,  Zhen Wang 3,  Yanfang Liu 2 4,  Zaoqu Liu 5,  Wanshun Li 1,  Yue Liu 1,  Chang Wu 1,  Liqi Sun 1,  Fei Jiang 1,  Hui Jiang 4,  Xiaoju Su 1,  Lisi Peng 1,  Jiayu Li 1,  Xinyue Wang 1,  Hua Yin 6,  Dongling Wan 1,  Yuyan Zhou 1,  Xiaorong Tian 1,  Shiyu Li 7,  Zhendong Jin 1 2,  Baoan Ji 8,  Zhaoshen Li 1 2,  Haojie Huang 1 2
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Changhai Hospital, Shanghai, 200433, China.
  • 2 National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
  • 3 Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • 4 Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
  • 5 Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
  • 6 Department of Gastroenterology, General Hospital of Ningxia Medical University, Ningxia Hui Autonomous Region, Yinchuan, 750004, China.
  • 7 Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 8 Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA.
PMID: 39887620 DOI: 10.1002/advs.202412282
Abstract

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.

Keywords

HIF1‐α; autoimmune pancreatitis; single‐cell atlas; visfatin.

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