Wilson MS, Ramalingam TR, Rivollier A et al. Gastroenterology 2011;140:254–64.
Interleukin-13 (IL-13) is one of the key cytokines of the Th2 immune response, which is prominent in ulcerative colitis. In this study, IL-13 was shown to negatively regulate the Th1/Th17 response by decreasing interferon-γ and IL-17A production.
The bioactivity of interleukin-13 (IL-13) is controlled by the IL-13rα2 decoy receptor. In this study, it was found that genetic deletion of IL13rα2 resulted in increased IL-13 activity. In piroxicam-induced colitis in IL10-deficient mice (which are susceptible to colitis development), loss of IL13rα2 resulted in reduced inflammation associated with reduced frequency of Th1/Th17 cytokine-, interferon-γ (IFN-γ)-, and IL-17A-secreting cells from mesenteric lymph node populations. In a separate Th2-dependent model of colitis mediated by infection with the helminth Trichuris muris, loss of IL13rα2 was also protective (100% mortality at <40 days in IL10–/– mice vs. 20% mortality at 100 days in IL10–/– IL13rα2–/– double-knockout mice). The double-knockout mice displayed enhanced IL-13 effector function compared with IL10–/– single-knockout mice, with increased goblet cells, mucus production, and tissue eosinophilia, and diminished IFN-γ/IL-17 production. The authors showed that, in vitro, Th17 cells expressed IL-13 receptors. Treatment with IL-13 reduced IL-17A production by this subset of cells in a dose-dependent fashion. Finally, treatment with neutralizing IL-13 antibodies significantly worsened inflammation and mortality rates in IL10–/– IL13rα2–/– double-knockout mice in the T muris infection colitis model, confirming the protective role anti-inflammatory role of IL-13.