Gut mucosal and female reproductive tract NK cells. NK cells found in the gut mucosa and FRT during the naive state exhibit an immature phenotype being in mice and CD16− in humans and resemble those NK cells found as residents in secondary lymphoid organs such as mesenteric lymph node (MLN) for the gut (top) and Iliac lymph node (ILN) for the FRT (bottom). This may suggest that gut and FRT resident NK cells are derived from NK precursors (NKP, pink), which migrate from bone marrow to lymph nodes (LN), where they differentiate into immature NK cells (iNK, blue cell in MLN, orange-red transition cell ILN). Dendritic cells (DC) draining from the lamina propria of the gut (CD103+) or DC from the FRT to the LN interact with immature NK cells and imprint the tissue address (α4β7/CCR9 for gut mucosa) that permits iNK cell homing to the correct tissues. In gut, NK cells can be IELs (orange cells) or in the LP (green cell) and respond to infectious pathogen (red circles) activated DCs and cytokine milieu in the tissue microenvironment becomes activated to produce IFNγ, IL-17, and/or CTL activity. In FRT, uterine NK cells (uNK, orange cell) have to balance help with fetal implantation via trophoblast recruitment, vascularization, and tolerance with ability to respond to pathogens. If stimulation of NK cells in response to a pathogen is high enough, IFNγ is expressed and may result in loss of pregnancy. Vaginal NK cells (iNK, brown) play an important role in containing invading pathogens via IFNγ production.
