Human placental trophoblast cells contribute to maternal-fetal tolerance through expressing IL-35 and mediating iT<sub>R</sub>35 conversion.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31601798.
- Also identified by DOI 10.1038/s41467-019-12484-z and PMC identifier 6787064.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
During pregnancy, trophoblast cells sustain the maternal-fetal tolerance via expressing and secreting various chemokines and cytokines. Our previous study revealed the expression of interleukin-35 (IL-35) in human first-trimester trophoblasts. Here we show that IL-35 is expressed in both human first-trimester primary trophoblast cells and a trophoblast cell line. Trophoblast cells inhibit the proliferation of human naive conventional T cells (T<sub>conv</sub> cells) and convert suppressed T<sub>conv</sub> cells into iT<sub>R</sub>35 in an IL-35-dependent manner. Mechanistically, trophoblast cell derived IL-35 mediates its function through phosphorylation of STAT1 and STAT3. In vivo studies confirm that mice with immunologically spontaneous abortion have lower levels of IL-35 and iT<sub>R</sub>35 cells at the maternal-fetal interface, and neutralizing anti-IL-35 mAb enhances abortion rates. Meanwhile, exogenous IL-35 induces iT<sub>R</sub>35 and prevents immunological abortion. Our findings thus suggest that trophoblast cells have a critical function in preserving maternal-fetal tolerance via secreting IL-35 during pregnancy.
Medical subject headings
- Interleukins
- Maternal-Fetal Exchange
- T-Lymphocytes, Regulatory
- Trophoblasts