Repressing IL-3-induced M2 macrophages through inhibiting IL-4 production from basophils. (A) IL-3 and GM-CSF stimulate the production of more IL-4 from SHIP−/− than SHIP+/+ Lin- BM cells. SHIP+/+ and SHIP−/− Lin- BM cells were cultured with M-CSF, IL-3, or GM-CSF for 24 h and supernatants were subjected to IL-4 ELISAs. Data shown are the means ± SEM of duplicate determinations. *, p < 0.05 compared with unstimulated cells. (B) Model of IL-3-induced M2 skewing and the role that SHIP plays in this process. IL-3 stimulates the proliferation and differentiation of both basophil precursors and monocyte/macrophage progenitors. IL-3 also stimulates the production of IL-4 from basophils and basophil progenitors in a STAT5-dependent manner. SHIP within the basophils represses this IL-4 production. The secreted IL-4, in turn, skews, via STAT6, the maturing and mature MΦs to an M2 phenotype. Copyright 2009. The American Association of Immunologists, Inc. .