PMC

α-Fetoprotein (AFP) did not directly affect the cytolytic activity of natural killer (NK) cells and soluble factor from dendritic cells (DCs) played a role in the inhibition of NK activity. (a) NK cells were cultured with AFP (25 µg/ml, □, AFP-NK cells) or albumin (Alb) (25 µg/ml, ◊, Alb-NK cells) or cultured with AFP-DCs () or Alb-DCs (♦) for 24 h. We evaluated the cytolytic activity of AFP-NK cells and Alb-NK cells or NK cells stimulated by AFP-DCs or Alb-DCs using K562 cells as target cells by ⁵¹Cr-releasing assay. We analysed statistically between the cytolytic activity of NK cells co-cultured with AFP-DCs () and Alb-DCs (♦) or between that of AFP-NK cells (□) and Alb-NK cells (◊). *P < 0·05 versus the cytolytic activity of NK cells cultured with Alb-DCs, #P < 0·05 versus the cytolytic activity of Alb-NK cells. (b) Enriched NK cells were co-cultured with AFP-DCs (□) or Alb-DCs (◊) for 24 h in the presence of 0·4 µm of inserting membrane (Transwell). NK cells were harvested and subjected to examine the cytolytic activity against K562 cells by ⁵¹Cr-releasing assay. *P < 0·05 versus the cytolytic activity of NK cells cultured with Alb-DCs. Representative results are shown. Similar results were obtained from three independent experiments in all experiments.

Construction of a prognostic model for genes associated with LUAD’s cytolytic activity. (a,b) Lasso regression was used to construct a prognostic Cytolytic activity-related prognostic model. (c) Model gene coefficient map. (d) Survival analysis of TCGA training set model. (e) Survival analysis of TCGA test set model (Yellow: High expression; Blue: Low expression).

Cytolytic NK cells may be targeted in preeclampsia. Induction of non-cytolytic NK cells and inhibition of cytolytic NK cells is one potential avenue for the treatment and prevention of preeclampsia. Anti-TLR5, anti-IL-6, and anti-CD28 inhibit IL-6’s activation of pro-apoptotic cytolytic type 1 NK cells. Anti-CD28 also directly inhibits type 1 NK cells, and promotes non-cytolytic, type 2 NK cells and the anti-apoptotic cytokines IL-10 and IFN-γ. 17-OHPC works similarly to promote type 2 NK cells. Together, these reduce the cytolytic NK cell response, which can lead to improper placentation and subsequent preeclampsia. 17-OHPC, 17-hydroxyprogesterone caproate; anti, antibody; IFN-γ, interferon gamma; NK2, non-cytolytic, type 2 Natural Killer cells; IL, interleukin; NK1, cytolytic, type 1 Natural Killer cells; TNF-α, tumor necrosis factor alpha; TLR5, toll like receptor 5. Created with https://biorender.com.

Cytolytic mechanisms utilized by cyTreg to modulate immune responses. (A) Granzyme perforin pathway. (B) Fas/FasL pathway (top), TRAIL/TRAILR pathway (middle), TNFα/TNFR pathway (bottom). Spi6, Serpin protease inhibitor 6; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; TRAILR, tumor necrosis factor-related apoptosis-inducing ligand receptor; DR5, death receptor; TNFα, tumor necrosis factor alpha; TNFR, TNFR, tumor necrosis factor receptor; Bid, BH3 interacting-domain death agonist; tBid, truncated Bid; FADD, Fas-associated protein with death domain; TRADD, TNFRSF1A associated via death domain; NF-kB, nuclear factor kappa B; DISC, death-inducing signaling complex.