Phenotypically similar but functionally distinct NK cell populations within the human maternal-fetal interface

Area of Science:

• Immunology
• Reproductive Biology
• Maternal-Fetal Medicine

Background:

• Natural killer (NK) cells are crucial for early human placentation and immune tolerance.
• The functional maintenance of NK cells throughout pregnancy remains poorly understood.
• NK cells exhibit diverse tissue-specific functions beyond cytotoxicity.

Purpose of the Study:

• To investigate the effector functions of NK cells at the decidual-placental interface (DPI) in full-term human pregnancies.
• To determine if NK cells maintain tolerance-like properties during pregnancy.
• To compare NK cell function in adjacent tissues within the maternal-fetal environment.

Main Methods:

• Isolation of NK cells from the decidual-placental interface and decidua of term human pregnancies.
• Assessment of NK cell effector function, specifically interferon-gamma (IFN-γ) production, in response to activating cytokines (IL-12, IL-15, IL-18).
• High-parameter flow cytometry and single-cell sequencing to analyze NK cell phenotype and transcriptomic profiles.

Main Results:

• NK cells from the DPI showed a significant lack of IFN-γ production upon cytokine stimulation.
• NK cells isolated from the decidua retained their responsiveness to cytokine activation.
• Tissue-resident CD103+CD69+ NK cells in DPI and decidua displayed distinct effector functions, not predictable by phenotype or transcript.

Conclusions:

• Distinct functional populations of resident NK cells exist at the human decidual-placental interface and in the decidua.
• NK cell function at the maternal-fetal interface is tissue-specific and dynamic during pregnancy.
• Functional specialization of NK cells may contribute to successful pregnancy maintenance.