02523nas a2200277   4500000000100000008004100001260001500042653001700057653001300074653002500087653002800112653001900140100001900159700002500178700001700203700001900220700002400239700002300263700002000286245015300306856007200459300001100531490000800542520168100550022001402231       2025                            d  c2025-01-0110aanimal model10aNK cells10aNatural killer cells10aPsychological stressors10aSex dimorphism1 aAlexis R. Katz1 aMargaret P. Huntwork1 aJay K. Kolls1 aJenny L. Hewes1 aCalder R. Ellsworth1 aRobert D. E. Clark1 aJohn C. Carlson00aImpact of psychological stressors on natural killer cell function: A comprehensive analysis based on stressor type, duration, intensity, and species  uhttps://www.sciencedirect.com/science/article/pii/S0031938424002828  a1147340 v2883 aPatients with natural killer (NK) cell deficiency or dysfunction are more susceptible to infections by Herpesviridae viruses, herpesvirus-related cancers, and macrophage activation syndromes. This review summarizes research on NK cell dysfunction following psychological stress, focusing on stressor type, duration, age of exposure, and species studied. Psychological stressors negatively affect NK cell activity (NKCA) across species. Prolonged stress leads to more significant decreases in NK cell number and function, with rehabilitation efforts proving ineffective in reversing these effects. Early life and prolonged stress exposure particularly increases the risk of infections and cancer due to impaired NKCA. The review also highlights that stress impacts males and females differently, with females exhibiting a more immunosuppressed NK cell phenotype. Notably, mice respond differently compared to humans and other animals, making them unsuitable for NK cell stress-related studies. Most studies measured NKCA using cytolytic assays against K-562 or YAC-1 cells. Although the exact mechanisms of NK cell dysfunction under stress remain unclear, potential causes include reduced release of secretory lysosomes with perforin or granzyme, impaired NK cell synapse formation, decreased expression of synapse-related molecules like CD2 or LFA-1 (CD11a), altered activating receptor expression, and dysregulated signaling pathways, such as decreased Erk1/2 phosphorylation and NFkB signaling. These mechanisms are not mutually exclusive, and future research is needed to clarify these pathways and develop therapeutic interventions for stress-induced immune dysregulation.  a0031-9384