STAT5b Isoform Controls IgE-mediated Mast Cell Function

Abstract Signal Transducers and Activators of Transcription (STATs) are latent transcription factors that control survival, proliferation and many other cellular functions. This protein family consists of seven members, including the closely related STAT5A and STAT5B, which show 96% amino acid sequence homology. We previously found that Stat5B is required for IgE-mediated cytokine production by mast cells in vitro, but have not tested in vivo correlates to this finding. In the current study, we show that Stat5B deficiency (KO) reduces IgE-induced passive systemic anaphylaxis (PSA) and IL-13 secretion in vivo, without altering mast cell tissue distribution. These results were corroborated by reduced PSA in response to anti-FceRI antibody injection. However, we were surprised to find that reduced PSA was not matched by lower plasma histamine levels. Further investigation revealed that Stat5B KO mice have a >5-fold increase in basal IgE levels and are hyperresponsive to histamine-induced anaphylaxis. These data support the conclusion that Stat5B is critical for IgE-induced mast cell activation in vivo, but also indicate that it contributes to basal IgE production and suppresses vascular responses to histamine. Thus Stat5B is involved in several overlapping aspects of the systemic mast cell response that warrant further study.