Down-regulation of NFIX is responsible for the weaker proliferation, and migration abilities and higher inflammatory level of fibroblasts from immunoglobulin G4-related sialadenitis based on RNA-sequence analysis
IgG4-related sialadenitis (IgG4-RS) is a type of immune-mediated systemic disease involving the salivary glands, yet its pathogenesis remains poorly investigated. The present study isolated primary FB from patients with IgG4-RS and healthy controls (n=3), designated as FB/IgG4-RS and FB/control, respectively. A total of 721 differentially expressed genes (DEGs) were identified in FB/IgG4-RS. These DEGs were implicated in various biological processes relevant to IgG4-RS development and several inflammation-related pathways. FB/IgG4-RS exhibited reduced proliferation and migration abilities, along with heightened inflammation levels compared to FB/control. Overexpression of NFIX significantly enhanced the proliferation and migration abilities of FB/IgG4-RS, decreased mRNA levels of IL6 and IL1B, and suppressed the NF-KB pathway. Conversely, NFIX knockdown in FB/control produced opposite effects. In conclusions, this study identified a distinct phenotype of FBs in IgG4-RS patients characterized by reduced proliferation and migration abilities, as well as heightened inflammation levels. The downregulation of NFIX appears pivotal in shaping the specific FB phenotype observed in IgG4-RS.