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

Abstract

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.