Mucosal IL‐10 and IL‐10 receptor expression patterns in paediatric patients with ulcerative colitis

Abstract

Interleukin-10 (IL-10) is a key anti-inflammatory cytokine. We aimed to assess IL-10 and IL-10 receptor (IL-10R) expression in the gut, and determine whether these patterns are altered in patients with ulcerative colitis (UC). Formalin-fixed paraffin-embedded rectal and transverse colon sections were collected from three groups of patients: (a) control subjects with normal colonoscopy and without history of inflammatory bowel disease; (b) UC patients with extensive colitis or pancolitis (E3/E4 phenotype); and (c) UC patients with limited distal disease (E1/E2 phenotype; n = 8-10 subjects per group). Immunohistochemistry (IHC) was performed to assess expression patterns of IL-10, IL-10R1 and IL-10R2, and was correlated with clinical, endoscopic and histologic severity indices among patients. A trend towards increased IL-10 expression was noted in rectal biopsies of patients with active UC, compared with controls. Moreover, IL-10 levels were significantly increased in transverse colon biopsies of patients with extensive/pancolitis, compared with control subjects and patients with limited distal disease. Rectal IL-10R1 and IL-10R2 levels were comparable between control subject and patients with active UC. However, transverse colon IL-10R1 levels were significantly higher in patients with E3/E4 colitis, compared with controls. Finally, we found no correlation between clinical, endoscopic and histologic severity of inflammation among UC patients and IL-10, IL-10R1 or IL-10R2 expression in rectal sections. Mucosal expression patterns of IL-10 and IL-10R, evaluated by IHC, were overall similar between control subjects and patients with active UC. Given IL-10's anti-inflammatory properties, additional studies are required to determine whether signalling through the IL-10R is altered among these patients.

IL-3 receptor signalling suppresses chronic intestinal inflammation by controlling mechanobiology and tissue egress of regulatory T cells

“…However, one has to consider that active inflammation also triggers regulatory pathways, which limit tissue destruction and may lead to resolution of inflammation. 36 Consistently, increased expression of the key Treg cytokine IL-10 and an increased presence of functional Tregs in active IBD have earlier been demonstrated 29 37 and IL-3 was strongly correlated with Treg cytokines and abundance. However, in the inflammatory network present in the mucosa in IBD, such compensatory attempts fall short of controlling disease due to an even more pronounced expansion of pro-inflammatory signalling and cells.…”

“…Indeed, the expression of IL3 mRNA in the colon of patients with IBD was significantly correlated with Treg cytokines such as IL10 or TGFB , 29 but not with pro-inflammatory mediators such as IL13 or IL18 ( figure 7F , online supplemental figure 10 ). Similarly, when we stained colon samples from patients with IBD for CD4 + Foxp3 + Tregs and for IL-3 + cells, we observed a strong correlation ( figure 7G ), which was consistent with the idea that IL-3 promotes mucosal residence of Tregs also in the human gut.…”

Propensity score analysis the clinical characteristics of active distal and extensive ulcerative colitis: a retrospective study

“…However, when inflammation occurs, the expression of IL-10 in the inflammatory and non-inflammatory areas of intestinal mucosa is significantly increased to play an anti-inflammatory role ( Melgar et al, 2003 ). In addition, studies show IL-10 and IL-10R1 levels were increased in transverse colon biopsies of patients with extensive/pancolitis, compared with control subjects and patients with limited distal disease ( Wittmann Dayagi et al, 2021 ). On 6 July 2022, Applied Molecular Transport (AMT) announced the results of the 2-stage MARKET test IL-10 inhibitor in patients with moderate to severe ulcerative colitis.…”

Involvement of gut microbiota recovery and autophagy induction in Youhua Kuijie formula’s protection against experimental ulcerative colitis

“…1E). Inflammatory factor IL-1β, IL-6, IL-17 and IL-10 are the key indicators used to evaluate UC-related inflammation in clinical and basic research [23,24]. Besides, the concentrations of these inflammatory cytokines in serum and colon tissues were also detected using corresponding commercial ELISA kits.…”