Functional IKK/NF-κB signaling in pancreatic stellate cells is essential to prevent autoimmune pancreatitis.

ABSTRACT: Pancreatic stellate cells (PSCs) are resident cells in the exocrine pancreas which contribute to pancreatic fibrogenesis and inflammation. Studies on NF-κB in pancreatitis so far focused mainly on the parenchymal and myeloid compartments. Here we show a protective immunomodulatory function of NF-κB in PSCs. Conditional deletion of NEMO (IKKγ) in PSCs leads to spontaneous pancreatitis with elevated circulating IgM, IgG and antinuclear autoantibodies (ANA) within 18 weeks. When further challenged with caerulein, NEMO^ΔCol1a2 mice show an exacerbated autoimmune phenotype characterized by increased infiltration of eosinophils, B and T lymphocytes with reduced latency period. Transcriptomic profiling shows that NEMO^ΔCol1a2 mice display molecular signatures resembling autoim

SUBMITTER: Chan LK 

PROVIDER: S-EPMC9142538 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature