Natural killer (NK) cells in bipolar disorders

Neuroinflammation and peripheral immune dysregulations, affecting both innate and adaptive immune responses, have repeatedly been demonstrated in bipolar disorder (BD). Given the increased susceptibility to infections, the chronic inflammation and autoimmune processes, abnormalities affecting the natural killer (NK) cells compartment are likely to play an important role in the pathophysiology of BD. We here address this question by describing current knowledge regarding phenotypic and functional characteristics of NK cells in BD in the context of well-established environmental risk factors as well as crosstalk between NK cells and other immune cells. Patients with BD show a permanent activation of NK cells along with a specific expansion of a cell subset, called “adaptive NK cells”, usually associated with several viral infections. We thus discuss the putative role of non-resolved infectious events in BD, possibly arising from suboptimal, genetically determined, anti-infectious responses or from yet to be identified other pathophysiological processes. The observed deregulation of NK cells in patients with BD may contribute to impaired immune functions, heightened inflammation, neuro-immune damage as well as cognitive decline and resistance to treatment, thus stressing the need of a deeper analysis of these immune cells in BD.