Interleukin-28A induces epithelial barrier dysfunction in CD patient-derived intestinal organoids

IL-28A levels were significantly increased in the plasma and biopsies from active patients with CD as compared with healthy subjects. IFN-γ exposure stimulated IL-28A expression in intestinal organoids. Partially mimicking the effect of IFN-γ, IL-28A impaired epithelial barrier function and disrupted junctional components through the activation of JAK-STAT1 signaling, whereas JAK1 inhibitor ameliorated the above-mentioned effects of IL-28A. These findings highlight the newly identified cytokine IL-28A as a novel contributor to CD pathogenesis and could be a putative target for CD treatment. We also provide new evidence for potential applications of JAK inhibition in CD therapy.