IL33 enhanced differentiation and function of alternatively activated macrophage and regulatory T cell

Abstract

IL33, a young member of the IL1 superfamily of cytokines, has been regarded as an important mediator of type II immune responses since it was discovered. Thereafter, more and more studies have demonstrated its multi-task role in homeostasis, wound healing and parasite clearance. IL33 could induce production of type II cytokines, such as IL10, IL5 and IL13, and consequently initiate the polarization of alternatively activated macrophages. Recently, the direct role of IL33 in promoting the differentiation and function of regulatory T cells (Treg) has also been reported. However, few studies examined the effects of IL33 on the interaction between alternatively activated macrophages and Treg, though studies about their reciprocal relationship have been started for decade. In this study, I reported the pivotal role of IL33 in regulating the interaction between alternatively activated macrophages and Treg through in vitro experiments. In addition, when IL33 combined with IL4, this dual cytokine could promote the polarization of alternatively activated macrophages, and augment its capacity to produce TGF-β. Through alternatively activated macrophages, IL33 could induce Treg differentiation while inhibit the activity of other T effector cells. On the other hand, IL33 could directly amplify the differentiation, activity and stability of Treg. Such activated Treg could enhance the immunosuppressive effects of alternatively activated macrophages through TGF-β production. In conclusion, my study showed that IL33 induced a positive feedback loop between alternatively activated macrophages and Treg, which in turn contributed to the summative immunosuppressive responses.