Stat5a is essential for the proliferation and survival of murine mast cells.
The regulatory role of signal transducer and activator of transcription (Stat) 5a in the proliferation and survival of mast cells was determined using Stat5a-deficient (Stat5a(-/-)) mice. First, although the mast cells in Stat5a(-/-) mice were morphologically indistinguishable from those in wild-type (WT) mice, the number of peritoneal mast cells was significantly decreased in Stat5a(-/-) mice as compared with that in WT mice. Furthermore, the interleukin-3 (IL-3)-dependent development of bone marrow-derived mast cells (BMMCs) was markedly decreased in Stat5a(-/-) mice. Second, IL-3-induced but not stem cell factor (SCF)-induced proliferation of BMMCs was significantly diminished in Stat5a(-/-) mice as compared with that in WT mice. Moreover, survival rates of both peritoneal mast cells and BMMCs were significantly decreased with increased apoptotic cells in Stat5a(-/-) mice as compared with those in WT mice. Finally, mRNA of Bcl-x(L) was induced after IL-3 stimulation in WT BMMCs but not in Stat5a(-/-) BMMCs, which may account for the accelerated apoptosis in Stat5a(-/-) mast cells. These results indicate that Stat5a plays an important role in mast cell development, proliferation, and survival.