4.7 Review

Immune Tolerance of the Human Decidua

Journal

JOURNAL OF CLINICAL MEDICINE
Volume 10, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/jcm10020351

Keywords

endometrium; immune tolerance; endometrial stromal cells; uterine natural killer cells; regulatory T cells (Treg); macrophages; heart; and neural crest derivatives-expressed protein 2 (HAND2); interleukin-15 (IL15); galectin 9

Funding

  1. Japan Society for the promotion of Science (JSPS) KAKENHI grant [17K11260, 19K06891]
  2. Setsuro Fujii memorial Foundation
  3. Takeda Science Foundation
  4. Grants-in-Aid for Scientific Research [17K11260, 19K06891] Funding Source: KAKEN

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The endometrium is essential for implantation, placental development, and successful pregnancy, undergoing cycles of proliferation, differentiation, and shedding. Immune cells in the endometrium, with conflicting functions of protection and tolerance towards the embryo, are significantly influenced by progesterone. Key molecules like interleukin-15 play pivotal roles in immune tolerance and pregnancy establishment.
The endometrium is necessary for implantation, complete development of the placenta, and a successful pregnancy. The endometrium undergoes repeated cycles of proliferation, decidualization (differentiation), and shedding during each menstrual cycle. The endometrium-including stromal, epithelial, vascular endothelial, and immune cells-is both functionally and morphologically altered in response to progesterone, causing changes in the number and types of immune cells. Immune cells make up half of the total number of endometrial cells during implantation and menstruation. Surprisingly, immune tolerant cells in the endometrium (uterine natural killer cells, T cells, and macrophages) have two conflicting functions: to protect the body by eliminating pathogenic microorganisms and other pathogens and to foster immunological change to tolerate the embryo during pregnancy. One of the key molecules involved in this control is the cytokine interleukin-15 (IL-15), which is secreted by endometrial stromal cells. Recently, it has been reported that IL-15 is directly regulated by the transcription factor heart- and neural crest derivatives-expressed protein 2 in endometrial stromal cells. In this review, we outline the significance of the endometrium and immune cell population during menstruation and early pregnancy and describe the factors involved in immune tolerance and their involvement in the establishment and maintenance of pregnancy.

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