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Changes in the Th1:Th2 Cytokine Balance During pregnancy at the Maternal-conceptus Interface in Pigs

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영어

It has been established that a shift from the T helper 1 (Th1) cytokine profile to the T helper 2 (Th2) profile during pregnancy contributes to the successful pregnancy. Interleukin-12 (IL12) is a Th1 cytokine composed of IL12A and IL12B and activates the JAK-STAT pathway and promotes Th1 cell development by binding heterodimeric receptors, IL12RB1 and IL12RB2. Interleukin-10 (IL10), a well-known Th2 cytokine, regulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on immune cells via heterotetramer receptor composed of IL10RA and IL10RB. Although the Th1:Th2 cytokine balance for the maintenance of pregnancy is well studied in humans and rodents, expression and function of IL12 and IL10 are not fully understood in pigs. Thus, this study determined expression of IL12, IL10 and their receptors at the maternal-conceptus interface in pigs. Real-time RT-PCR analysis showed levels of IL12A and IL12B mRNAs in the uterine endometrium were high during early pregnancy, but maintained low expression levels thereafter. Levels of IL12RB1 mRNA during pregnancy showed a biphasic pattern with the highest levels on D15 and D60 of pregnancy, while levels of IL12RB2 mRNA did not change during pregnancy. Levels of IL10 mRNA in the uterine endometrium were highest on D15 of pregnancy and decreased toward term pregnancy. Levels of IL10RA mRNA showed highest levels on D30, while levels of IL10RB mRNA were biphasic with highest levels on D12 and D30 of pregnancy. Immunohistochemical analysis showed that IL12 protein was localized specifically to scattered cell types in endometrial stroma during the estrous cycle and early pregnancy. IL10 protein was detected on scattered cells around the blood vessels in the endometrium during early pregnancy, then detected in all endometrial stroma during mid- to late pregnancy. Conceptus and chorioallantoic tissues during pregnancy also expressed IL12, IL10 and their receptors. These results showed that there were changes in IL12 and IL10 expression in the uterine endometrium during pregnancy, suggesting that a shift toward IL10, a Th2 cytokine, over IL12, a Th1 cytokine, occurs at the maternal conceptus interface for the successful establishment of pregnancy in pigs.

저자정보

  • Jisoo Han Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea
  • Inkyu Yoo Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea
  • Hwanhee Jang Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea
  • Soogil Chae Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea
  • Soohyung Lee Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea
  • Hakhyun Ka Division of Biological Science and Technology, Yonsei University, Wonju 26493, Republic of Korea

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