JEG-3 Trophoblast Cells Influence ILC-like Transformation of NK Cells In Vitro

Area of Science:

• Reproductive immunology
• Innate immunity
• Cellular and molecular immunology

Background:

• The uterine decidua hosts unique natural killer (NK) cells and other innate lymphoid cells (ILCs).
• ILC differentiation is governed by specific transcription factors: T-bet for ILC1, RORα and GATA3 for ILC2, and RORγt and AhR for ILC3.

Purpose of the Study:

• To investigate the in vitro effects of trophoblast cells and cytokines on NK cell transcription factor expression and cytotoxic activity.
• To determine how trophoblast cells influence NK cell differentiation towards ILC phenotypes.

Main Methods:

• Co-culture of NK-92 and JEG-3 cell lines with cytokines (IFNγ, IL-10, IL-15, TGFβ).
• Analysis of transcription factor expression (AhR, Eomes, GATA-3, RORα, RORγt, T-bet) using antibody treatment.
• Assessment of NK cell cytotoxicity against K562 cells.
• Measurement of trophoblast secretion of TGFβ and βhCG.

Main Results:

• Trophoblast co-culture decreased NK cell expression of Eomes, T-bet, RORα, and AhR, while RORγt remained unchanged.
• IFNγ inhibited AhR expression; IL-10 increased T-bet+ ILC1-like cells.
• IL-10 and IFNγ suppressed NK cell RORα expression and stimulated trophoblast TGFβ secretion.
• NK cell cytotoxicity was reduced after co-culture with trophoblast cells.

Conclusions:

• Trophoblast cells significantly influence NK cells, promoting the acquisition of ILC1 and ILC3 characteristics.
• This interaction modulates NK cell effector functions and transcription factor profiles within the uterine decidua.