IL-33 deficiency protects mice from DSS-induced experimental colitis by suppressing ILC2 and Th17 cell responses.

BACKGROUND

Recently, IL-33-driven ILC2 response has been shown to participate in a variety of diseases. However, IL-33-driven ILC2 immunity has not been extensively characterized in the context of colitis yet.

MATERIALS AND SUBJECTS

The RAG-2- and IL-33-deficient mice were used to investigate the role and underlying mechanisms of IL-33-driven ILC2 response in the DSS-induced experimental colitis. Body weight, length of colon, and histological analysis were monitored to evaluate the severity of colitis. Proportions of immune cells were examined by flow cytometry. Levels of cytokines were analyzed by ELISA and q-PCR.

RESULTS

Administration of exogenous IL-33 aggravated the DSS-induced colitis, which revealed that IL-33 promoted the generation of ILC2 cells to mediate the inflammation of colon. Consistently, this effect was confirmed in RAG-2-deficient mice without T, B cells. Furthermore, IL-33-deficient mice were used to examine the role of endogenous IL-33 on the pathogenesis of DSS-induced colitis. Interestingly, lack of endogenous IL-33 protected the mice from the DSS-induced colitis. The protective effect is associated with impairments of development of ILC2 as well as Th17 cells. Analysis of their cytokine production profiles revealed that IL-33 deficiency resulted in the reduction of cytokines IL-6 and IL-1β as well as IL-10. These results suggest that IL-33/ILC2 axis is a potential therapeutic target for human colitis.

CONCLUSION

Our findings demonstrate that IL-33 deficiency protects mice from DSS-induced colitis. The protective effect is associated with impairments of ILC2 and Th17 cell development as well as reduction of inflammatory cytokines IL-6 and IL-1β.