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.
Tomio
Ayako
A
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Schust
Danny J
DJ
Kawana
Kei
K
Yasugi
Toshiharu
T
Kawana
Yukiko
Y
Mahalingaiah
Shruthi
S
Fujii
Tomoyuki
T
Taketani
Yuji
Y
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053614:Janus Kinase 2 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011388:Prolactin / Q000494:pharmacology*; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology; D020825:T-Box Domain Proteins / Q000276:immunology*; D013997:Time Factors; D000098815:T-bet Transcription Factor
D050799:STAT5 Transcription Factor; D050826:Suppressor of Cytokine Signaling Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D011388:Prolactin; D053614:Janus Kinase 2