Recently, the original research article of “Human Placental Trophoblast Cells Contribute to Maternal-fetal Tolerance through Expressing IL-35 and Mediating iTR35 Conversion” completed by Professor Mao Haiting’s team from the Laboratory Medicine Center of the Second Hospital of Shandong University has been published online in Nature Communications (5-Year Impact Factor 13.811).
In this article, the Second Hospital of Shandong University is the first author affiliation and the corresponding author affiliation, Liu Jia and Hao Shengnan, doctoral students of the Laboratory Medicine Center, are the co-first authors, and Mao Haiting is the corresponding author.
It is learned that, as the only exception to the traditional immunological principle, maternal-fetal immune tolerance has always been the focus of attention in the field of reproductive immunology. The maternal immune system “recognizes” semi-allogeneic fetuses, and establishes a mechanism of immune tolerance, which is the key to ensuring a successful pregnancy. In order to maintain a successful pregnancy, cells and cytokines at the maternal-fetal interface must act synergistically to induce immune tolerance. However, the complex regulatory mechanism behind this unique immune behavior has not been fully revealed. Interleukin-35 (IL-35) is an inhibitory cytokine secreted by regulatory T cells (Treg), which can inhibit the proliferation of effector T cells and induce T cells to transform into IL-35-dependent regulatory T cells ( iTR35).
According to the previous researches conducted by Professor Mao Haiting’s team, in addition to Treg, human placental trophoblast cells from early pregnancy can also express and secrete IL-35. In this research, the research team further confirmed that IL-35 secreted by trophoblast cells can inhibit the proliferation of effector T cells at the maternal-fetal interface and induce the production of iTR35 cells, which contributes to the establishment and maintenance of the maternal-fetal local immune tolerance microenvironment.
Animal experiments showed that, compared with normal pregnant mice, the levels of IL-35 and iTR35 cells in the maternal-fetal part of immune spontaneous abortion mice are significantly lower than those in the normal pregnancy group. However, exogenous IL-35 treatment can induce the production of iTR35 cells and prevent the occurrence of spontaneous abortion. This research also conducted an in-depth analysis on the suppressive phenotype, cytokine expression profile and regulatory mechanism of T cells induced by trophoblast cell derived IL-35. The research results are of important significance and clinical application value for revealing the unique immune tolerance mechanism at the maternal-fetal interface and the choice of therapeutic drugs for clinically unexplained habitual abortion.
The above research has been funded by the General Project of the National Natural Science Foundation of China and the General Project of the Natural Science Foundation of Shandong Province.
Research Article Link:
https://www.nature.com/articles/s41467-019-12484-z
{Author: Liu Jia, Feng Yimin; Source: Laboratory Medicine Center; Editor: Publicity Department/News Center}