Interleukin (IL)-2 and IL-21 can drive alternative and sometimes opposing differentiation programs in a range of cell types, including stimulatory and inhibitory germinal center populations. This study reported that IL-2 contributes to the pathogenic role of IL-9 in lung disease and inflammation in cystic fibrosis through a self-amplifying circuit involving IL-2. In this circuit, lung epithelial damage resulted in the release of IL-33, which induced the expansion of innate lymphoid cells and their production of IL-9, which triggered mast cells to secrete IL-2. The mast cell-produced IL-2 then further expanded both CD25+ type 2 innate lymphoid cells as well as T helper type 9 (Th9) cells in the lung, promoting the ongoing inflammatory process. This Recommendation is of an article referenced in an F1000 Faculty Review also written by Rosanne Spolski, Daniel Gromer, and Warren J. Leonard.