The decidual stromal cells-secreted CCL2 induces and maintains decidual leukocytes into Th2 bias in human early pregnancy.
The precise mechanism of characteristic Th2 predominance at maternal-fetal interface remains unresolved. In the present study, we investigated roles of the decidua-derived CCL2 in Th2 predominance at maternal-fetal interface. FCM shows that 55% CD56(+)CD16(-)CD3(-) decidual NK, 52% CD4(+) T cells and 75% CD14(+) monocytes express CCR2. Recombinant human CCL2 (rhCCL2) and the decidual stromal cells (DSCs)-derived supernatant can enhance proliferation and inhibit apoptosis of these decidual leukocytes (DLCs), and promote Th2 cytokines production, IL-4 and IL-10, with an increase in GATA-3 transcription. They also inhibit the secretion of Th1 cytokines, TNF-α and IFN-γ, with a decrease in T-bet transcription It is concluded that the secreted CCL2 by decidual stromal cells increases GATA-3 transcription and decreases T-bet transcription in the decidual leukocytes, which contributes to Th2 polarization at maternal-fetal interface. Furthermore, the Th2 cytokines, IL-4 and IL-10, rather than Th1 cytokines, was shown to increase CCL2 secretion of DSC.
Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University Shanghai, 200011, China.
Yin-Yan
YY
He
Xiao-Ju
XJ
He
Pei-Fen
PF
Guo
Mei-Rong
MR
Du
Jun
J
Shao
Ming-Qing
MQ
Li
Da-Jin
DJ
Li
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D017077:Culture Media, Conditioned; D003656:Decidua / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D050990:GATA3 Transcription Factor / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D011261:Pregnancy Trimester, First; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic
D015703:Antigens, CD; C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D050990:GATA3 Transcription Factor; D054390:Receptors, CCR2; D011994:Recombinant Proteins