TGF-β induces ST2 and programs ILC2 development

The molecular pathways underlying the development of innate lymphoid cells (ILCs) are mostly unknown. Here we show that TGF-beta signaling programs the development of ILC2s from their progenitors. Specifically, the deficiency of TGF-beta receptor II in bone marrow progenitors results in inefficient development of ILC2s, but not ILC1s or ILC3s. Mechanistically, TGF-beta signaling is required for the generation and maintenance of ILC2 progenitors (ILC2p). In addition, TGF-beta 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-beta in the development of ILC2s from their progenitors.