TGF-β induces ST2 and programs ILC2 development
Li Wang, Jun Tang, Xia Yang, Peter Zanvit, Kairong Cui, Wai Lim Ku, Wenwen Jin, Dunfang Zhang, Nathan Goldberg, Alexander Cain, Bing Ni, Keji Zhao, Yuzhang Wu, Wanjun Chen
Abstract
The molecular pathways underlying the development of innate lymphoid cells (ILCs) are mostly unknown. Here we show that TGF-β signaling programs the development of ILC2s from their progenitors. Specifically, the deficiency of TGF-β receptor II in bone marrow progenitors results in inefficient development of ILC2s, but not ILC1s or ILC3s. Mechanistically, TGF-β signaling is required for the generation and maintenance of ILC2 progenitors (ILC2p). In addition, TGF-β upregulates the expression of the IL-33 receptor gene Il1rl1 (encoding IL-1 receptor-like 1, also known as ST2) in ILC2p and common helper-like innate lymphoid progenitors (CHILP), at least partially through the MEK-dependent pathway. These findings identify a function of TGF-β in the development of ILC2s from their progenitors.