Interleukin-26 Expression in Inflammatory Bowel Disease and Its Immunoregulatory Effects on Macrophages

Abstract

Background and AimInterleukin-26 (IL-26) has been implicated in several chronic inflammatory diseases. However, its role in inflammatory bowel disease (IBD) remains to be elucidated. We aimed to investigate IL-26 expression in IBD and its immunoregulatory effects on macrophages.MethodsWe assessed IL-26 expression in the intestinal mucosa and blood samples of IBD patients and healthy controls (HC). The associations between the clinical characteristics of IBD and IL-26 expression levels in serum and peripheral blood mononuclear cells (PBMCs) were investigated. In addition, the transcriptional changes in THP-1 macrophages exposed to IL-26 were determined by RNA sequencing and validated with qRT-PCR, ELISA and western blots.ResultsCompared with HC, in IBD patients, IL-26 expression levels were elevated in the inflamed intestinal mucosa, and reduced in serum and PBMCs. IL-26 mRNA levels in PBMCs, but not serum IL-26 levels, were inversely correlated with disease activity in IBD. Furthermore, IL-26 mRNA levels in PBMCs were significantly lower in patients with complicated Crohn’s disease. A total of 1,303 differentially expressed protein-coding genes were identified between untreated and IL-26-treated macrophages. The up-regulated genes showed enrichment in some inflammatory and immune-related processes and pathways. Additionally, GSEA showed that neutrophil, monocyte, and lymphocyte chemotaxis was significantly enriched in IL-26-treated macrophages. Further validation revealed that IL-26 promotes the secretion of multiple inflammatory cytokines and chemokines and upregulates the expression of adhesion molecules, MMP-8, and MMP-9 while inhibiting MMP-1 in macrophages.ConclusionCompared with HC, in IBD patients, IL-26 levels were elevated in the inflamed intestinal mucosa, and reduced in the peripheral blood. The transcriptional changes in macrophages exposed to IL-26 suggest that IL-26 may amplify the aberrant immune response in IBD by activating macrophages.

Increased interleukin-26 in the peripheral joints of patients with axial spondyloarthritis and psoriatic arthritis, co-localizing with CD68-positive synoviocytes

“…Differences between the serum levels of cytokines and local expression are not uncommon and have been described for example for IL-20 in patients with rheumatoid arthritis (40). This discrepancy has also been observed in patients with IBD, where increased protein and mRNA expression levels of IL26 in the gut were evident compared with HCs, but IL26 serum levels and IL26 expression in PBMCs were lower (41). This would fit with our observation of local IL26 attributable to tissue-resident CD68 + macrophage-like synoviocytes in SpA and not extravasated CD3 + T cells.…”

The role of Th17 cells in inflammatory bowel disease and the research progress

“…The upregulation of CCL20 expression and the occurrence of neutrophil production of neutrophil extracellular traps (NETs) further promotes the recruitment and activation of Th17 cells, leading to aggravation of the inflammatory response. IL-26 amplifies the aberrant inflammatory immune response; upregulates IL-6 and IL-8 expression through the STAT1, STAT3, PI3K/Akt, and MAPK signaling pathways; induces the adhesion molecules MMP-8 and MMP-9 expression; and activates macrophages ( 15 , 16 ).…”