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Background <p>Type 1 autoimmune pancreatitis (AIP) is pancreatic manifestation of IgG4-related disease (IgG4-RD), characterized by pancreatic lymphoplasmacytic infiltration. Despite this well-known pathological feature, the immune microenvironment and the complex cellular interactions within the pancreas in AIP remain poorly understood. This study aimed to characterize the local immune features of the pancreas in AIP patients.</p> Methods <p>We employed single-cell RNA sequencing (scRNA-seq), immune receptor repertoire sequencing (scTCR/BCR-seq), and spatial transcriptome sequencing on biopsy samples from lesion tissues of AIP patients. Flow cytometry, multicolour immunofluorescence, and functional assays were performed to validate the findings from bioinformatics analysis.</p> Results <p>Our results revealed an increased presence of IgD<sup>−</sup> age-associated B cells (ABCs) in the pancreas of AIP patients. These ABCs were predicted to differentiate into plasma cells that secrete IgG. Additionally, <i>CXCL9</i><sup>+</sup> macrophages were found to recruit IgD<sup>−</sup> ABCs via the CXCL9-CXCR3 axis. Elevated levels of T follicular helper cells (Tfhs) were also observed, which interacted with IgD<sup>−</sup> ABCs through IL-21 secretion. Both ABCs and Tfhs were localized at the periphery of pancreatic tertiary lymphoid structures (TLSs). Importantly, these immune abnormalities were specific to AIP and were not present in the pancreases of patients with chronic pancreatitis.</p> Conclusions <p>These findings highlight significant alterations in the pancreatic immune microenvironment in AIP and propose a potential pathogenic model involving ABCs, Tfhs, and macrophages. This model provides valuable insights that could inform the development of targeted therapeutic strategies for AIP.</p>

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Single-cell multi-omics analysis revealed the expansion of age-associated B cells in the pancreas of type 1 autoimmune pancreatitis patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月4日

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  • Jiaxin Wang,
  • Chenxiao Liu,
  • Xianda Zhang,
  • Tianyi Che,
  • Yizhou Zhao,
  • Qidi Yang,
  • Xianzheng Qin,
  • Yifei Chen,
  • Xiang Ao,
  • Xiaonan Shen,
  • Xiangyi He,
  • Tingting Gong,
  • Ling Zhang,
  • Minmin Zhang,
  • Dong Wang,
  • Yanhua Du,
  • Li Wen,
  • Youqiong Ye,
  • Yao Zhang,
  • Chunhua Zhou,
  • Duowu Zou

摘要

Background

Type 1 autoimmune pancreatitis (AIP) is pancreatic manifestation of IgG4-related disease (IgG4-RD), characterized by pancreatic lymphoplasmacytic infiltration. Despite this well-known pathological feature, the immune microenvironment and the complex cellular interactions within the pancreas in AIP remain poorly understood. This study aimed to characterize the local immune features of the pancreas in AIP patients.

Methods

We employed single-cell RNA sequencing (scRNA-seq), immune receptor repertoire sequencing (scTCR/BCR-seq), and spatial transcriptome sequencing on biopsy samples from lesion tissues of AIP patients. Flow cytometry, multicolour immunofluorescence, and functional assays were performed to validate the findings from bioinformatics analysis.

Results

Our results revealed an increased presence of IgD− age-associated B cells (ABCs) in the pancreas of AIP patients. These ABCs were predicted to differentiate into plasma cells that secrete IgG. Additionally, CXCL9+ macrophages were found to recruit IgD− ABCs via the CXCL9-CXCR3 axis. Elevated levels of T follicular helper cells (Tfhs) were also observed, which interacted with IgD− ABCs through IL-21 secretion. Both ABCs and Tfhs were localized at the periphery of pancreatic tertiary lymphoid structures (TLSs). Importantly, these immune abnormalities were specific to AIP and were not present in the pancreases of patients with chronic pancreatitis.

Conclusions

These findings highlight significant alterations in the pancreatic immune microenvironment in AIP and propose a potential pathogenic model involving ABCs, Tfhs, and macrophages. This model provides valuable insights that could inform the development of targeted therapeutic strategies for AIP.