Interleukin 15 in murine models of colitis

Abstract

Inflammatory bowel diseases (IBDs) are characterized by abnormal, non-antigen specific chronic inflammation of unknown etiology. Genome-wide association studies show that many IBD genetic susceptibility loci map to immune function genes and compelling evidence indicate that environmental factors play a critical role in IBD pathogenesis. Clinical and experimental evidence implicate the pro-inflammatory cytokine IL-15 in the pathogenesis of IBD. IL-15 and IL-15α expression is increased in the inflamed mucosa of IBD patients. IL-15 contributes to the maintenance of different cell subsets in the intestinal mucosa. However, very few studies have addressed the role of IL-15 in pre-clinical models of colitis. In this study, we use three well-characterized models of experimental colitis to determine the contribution of IL-15 to pathological intestinal inflammation.

Profibrogenic role of IL-15 through IL-15 receptor alpha-mediated trans-presentation in the carbon tetrachloride-induced liver fibrosis model

“…Il15 –/– and Il15ra –/– mice were back-crossed to C57BL/6J mice (Charles River, Canada) every four generations, and the three genotypes used in this study were established from these crosses. Analyses of gut microbiota of the three genotypes showed minimal differences ( 35 ). Mice were bred and housed in ventilated cages in the same housing unit throughout the experiment.…”

From anatomy to immunity in the gastrointestinal system

“…Their etiology is not fully understood but it is generally accepted that IBD have a multifactorial origin, with underlying genetic susceptibility awaken by environmental factors that perturb the intestinal homeostasis and trigger the onset of the diseases (Graham & Xavier, 2020). Using various animal models of colitis, Kautzman et al (2022) investigated the contribution of the pro‐inflammatory cytokine interleukin 15 (IL‐15) to intestinal inflammatory injury and the establishment of colitis. Studies in humans suggest an implication of IL‐15 in the immunopathogenesis of IBD and the results from Kautzman et al support that notion, suggesting that IL‐15 signaling, possibly in immune cells of the myeloid lineage, amplifies the damage of experimental colitis, although the effect shows a dependence on the colitis model used.…”