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.

NK cell detachment from target cells is regulated by successful cytotoxicity and influences cytokine production

Natural killer(NK)cells participate in early immune defenses against pathogens and tumors and play a major role as immune effector and regulatory cells.The NK cell-mediated elimination of an infected or cancerous cell is a highly regulated process that requires the formation of a cell contact,the establishment of an immunological synapse and the polarization and release of lytic granules.Additionally,the detachment of NK cells from target cells is important for NK cells to bind and kill other cells in a process called serial killing.However,very little is known about this detachment process.Here,we show that NK detachment is directly connected to the successful killing of a target cell.The inhibition of killing due to reduced NK cell cytotoxicity or increased target cell resistance results in defective detachment and prolonged contact times.This effect leads to sustained Ca^(2+) flux in NK cells and the hypersecretion of proinflammatory cytokines.Linking defective cytotoxicity with enhanced cytokine secretion via reduced detachment may explain inflammatory pathologies in several diseases.