Natural killer cells protect white matter integrity in bipolar disorder

Autor: Andrea Falini, Sara Di Toro, Francesco Benedetti, Benedetta Vai, Luca Battistini, Annamaria Finardi, Elisa M T Melloni, Giovanna Borsellino, Veronica Aggio, Sara Poletti, Cristina Colombo, Elena Manfredi, Roberto Furlan
Přispěvatelé: Furlan, Roberto, Melloni, Elisa, Finardi, Annamaria, Vai, Benedetta, Di Toro, Sara, Aggio, Veronica, Battistini, Luca, Borsellino, Giovanna, Manfredi, Elena, Falini, Andrea, Colombo, Cristina, Poletti, Sara, Benedetti, Francesco.
Rok vydání: 2019
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
Bipolar Disorder
Neuroimmunology
Immunology
chemical and pharmacologic phenomena
White matter
Interferon-gamma
Functional connectivity
03 medical and health sciences
Behavioral Neuroscience
0302 clinical medicine
Immune system
Neuroinflammation
Internal medicine
Fractional anisotropy
medicine
Humans
Interleukin 4
Innate immune system
Tumor Necrosis Factor-alpha
Endocrine and Autonomic Systems
Chemistry
Interleukin-17
Brain
hemic and immune systems
Middle Aged
Magnetic Resonance Imaging
White Matter
CD56 Antigen
Killer Cells
Natural
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Connectomic
Anisotropy
Female
Tumor necrosis factor alpha
030217 neurology & neurosurgery
Zdroj: Brain, Behavior, and Immunity. 81:410-421
ISSN: 0889-1591
DOI: 10.1016/j.bbi.2019.06.037
Popis: Background Bipolar Disorder (BD) associates with disrupted white matter (WM) microstructure and functional connectivity, and with a perturbation of the immune system. Higher cytokines, and reduced T cells, correlated with WM disruption and fMRI responses. A core component of the innate immune system, natural killer (NK) cells were detected in brain parenchyma, but never studied in BD. Methods We studied Diffusion Tensor Imaging (DTI) measures of water diffusion, fMRI corticolimbic functional response and connectivity, and multi-parameter cytofluorometry analysis of NK (CD56+) subpopulations, in 30 inpatients with active Bipolar Disorder type I. NK cells were also obtained in 36 healthy controls. Results Patients had significantly higher circulating counts of CD56+GMCSF+, CD56+INFγ+, and CD56+IL17+. NK cell levels positively associated to fractional anisotropy (FA) measures. CD56+TNFα+, CD56+INFγ+, and CD56+GMCSF+ directly correlated with FA, and inversely with radial (RD) and mean (MD) diffusivity. Duration of lithium treatment associated with higher CD56+TNFα+, CD56+IL2+, and CD56+IL4+, and positively associated with FA in tracts were NKs had significant effects. A mediation model suggested a partial mediation of CD56+TNFα+ cells, higher in patients on lithium, on the effects of lithium on FA. Frequencies of the same cytokine-producing NK cells also influenced fMRI cortico-limbic functional connectivity during processing of both, emotional and non-emotional stimuli. Discussion Higher circulating cytokine-producing NK cells associated with lithium treatment, and with DTI measures of WM integrity, partially mediating the effect of lithium on WM. The same cells associated with fMRI responses and connectivity, thus suggesting an effect on structural and functional connectomics in BD.
Databáze: OpenAIRE
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