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.
Highlights
The molecular pathways underlying the development of innate lymphoid cells (ILCs) are mostly unknown
We show that TGF-β signaling is required for the development of ILC2s from their progenitors, but not of ILC1s or ILC3s
To study whether TGF-β signaling affects the development of ILCs from their bone marrow (BM) progenitors, we created mixed BM chimeric mice in which CD45.2+ BM cells from tamoxifen- (Tgfbr2−/−) or oil-treated (Control) Tgfbr2f/fER-Cre+ mice in equal numbers were injected into lethally irradiated CD45.1+ hosts along with normal CD45.1+ BM cells at a 1:1 ratio, respectively (Tgfbr2−/−/ 45.1 vs. Control/45.1)
Summary
The molecular pathways underlying the development of innate lymphoid cells (ILCs) are mostly unknown. TGF-β upregulates the expression of the IL-33 receptor gene Il1rl[1] (encoding IL-1 receptor-like 1, 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. TGF-β promotes the development and maturation of ILC2s from their progenitors accompanied with an upregulation of ST2, which was at least partially regulated via MEK pathway. TGF-β is required for the maintenance of mature ILC2s in both physiological and pathological settings
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