Regulation of natural killer cell activity by glucocorticoids,serotonin,dopamine,and epinephrine

The immune system and the nervous system are highly complex organs composed of various different cells that must interact with each other for proper function of the system.This communication can be mediated by soluble factors.The factors released by the nervous system(neurotransmitters)differ from those released by the immune system(cytokines).Nevertheless,the nervous and immune systems can influence each other’s activity because immune cells express neurotransmitter receptors,and neurons express cytokine receptors.Moreover,immune cells can synthesize and release neurotransmitters themselves,thus using neurotransmittermediated pathways via autocrine and paracrine mechanisms.Natural killer(NK)cells are innate lymphocytes that are important for early and effective immune reactions against infections and cancer.Many studies have shown the strong influence of stress and the nervous system on NK cell activity.This phenomenon may be one reason why chronic stress leads to a higher incidence of infections and cancer.Here,we review the effects of neuroendocrine factors on the different activities of NK cells.Understanding the effects of neuroendocrine factors on NK cell activities during physiological and pathophysiological conditions may result in novel therapeutic strategies to enhance NK cell functions against tumors.

Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa

Genetic variation is a key factor influencing cytokine production capacity,but which genetic loci regulate cytokine production before and after vaccination,particularly in African population is unknown.Here,we aimed to identify single-nucleotide polymorphisms(SNPs)controlling cytokine responses after microbial stimulation in infants of West-African ancestry,comprising of low-birth-weight neonates randomized to bacillus Calmette-Gue rin(BCG)vaccine-at-birth or to the usual delayed BCG.Genome-wide cytokine cytokine quantitative trait loci(cQTL)mapping revealed 12 independent loci,of which the LINC01082-LINC00917 locus influenced more than half of the cytokine-stimulation pairs assessed.Furthermore,nine distinct cQTLs were found among infants randomized to BCG.Functional validation confirmed that several complement genes affect cytokine response after BCG vaccination.We observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European individuals.These data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations.