Prolactin can modulate CD4(+) T-cell response through receptor-mediated alterations in the expression of T-bet

Low-dose prolactin induces proinflammatory responses and antibody production, whereas high-dose prolactin suppresses these responses. Mechanisms for these opposing effects remain incompletely defined. We have previously demonstrated that T-bet, a key transcription factor directing T helper type 1 inflammatory responses, is regulated by female steroid hormones in human mucosal epithelial cells via Stat1 and 5 pathways. T-bet was also modulated in a CD4(+) T cell line by prolactin exposure. Prolactin rapidly induced T-bet transcription through phosphorylation of JAK2 and Stat5, but not Stat1. Phosphorylated Stat5 then bound to the T-bet regulatory region. These effects were weaker with high-dose prolactin exposures. Upon long-term prolactin exposure, low-dose prolactin induced T-bet expression, whereas high-dose prolactin tended to suppress it. Prolactin induced the suppressors of cytokine signaling (SOCS) 1 and 3 in a dose-dependent manner. With high-dose exposure, this was associated with an inhibition of the phosphorylation of T-bet regulatory region-bound Stat5. Further, the dose-dependent prolactin effects on T-bet expression were confirmed in murine primary CD4+ T cells. These data suggest that the divergent immune effects of low- and high-dose prolactin may involve modulation of T-bet and alterations in the balance of the prolactin/JAK2/Stat5 and the prolactin/SOCS1 and 3 pathways.