While IFN-γ and type I IFNs have been extensively studied and are known to participate in the pathogenesis of celiac disease (CeD), limited information is available regarding the role of type III IFNs.
The aim of this study was to evaluate the expression of the type III IFNs IFNL1 and IFNL2/3 and their receptor IFNLR in the small intestine of healthy individuals and patients with CeD, and to investigate their relationship with other IFNs and genes involved in IFN signaling pathways.
Duodenal biopsies were collected from untreated CeD patients and non-celiacs and analyzed by RT-qPCR, fluorescence microscopy, and flow cytometry. The study protocol was approved by the ethics committees of the health institutions.
RT-qPCR analysis of duodenal biopsies showed significant upregulation of IFNB1, IFNG, and the type III IFNs IFNL1 and IFNL2/3 in CeD patients compared with controls (p < 0.05). Interestingly, IFNL1 and IFNB1 mRNA levels showed a significant positive correlation (p < 0.05).
Several transcription factors and genes associated with IFN signaling were also significantly upregulated in CeD, including MX1, IRF1, STAT1, IRF3, IRF7, ISG15, USP18, and SOCS1 (p < 0.05). In contrast, STAT3 expression was significantly reduced, whereas IRF4, IRF8, and SOCS3 showed no significant differences between groups.
Immunofluorescence analysis of duodenal sections demonstrated the presence of type III IFNs in both the epithelial and lamina propria compartments of CeD patients. IFNL expression was significantly increased in both CD45⁺ cells and enterocytes in the duodenal epithelium of CeD patients (p < 0.05). Flow cytometry analysis showed reduced IFNLR expression on isolated EpCAM⁺ epithelial cells from CeD patients compared with controls.
Together, these findings support a potential role for type III IFN in the mucosal immune response in CeD and warrant further investigation of their contribution to disease pathogenesis.