Psychosis is a condition of the mind that has an important global prevalence and repre-sents a serious health problem, especially due to its incidence on young people and the risk of suicide for them. Its causes can be genetic and environmental, but it has been hypothesized the involvement of brain inflammation in the determining of the psychotic symptoms. For patients with Schizophrenia and Bipolar Disorder, it has been evidenced in the peripheral blood a higher level of pro-inflammatory cytokines, the increase of the circulating T cells and NK cells and the altered permeability of the Blood-Brain-Barrier. In addition, previous studies on the peripheral blood and post-mortem brain sections of patients with Bipolar Disorder I have shown an important reduction in the peripheral blood of T effector memory cells (TEM), Terminally Differentiated Effector Memory T cells (TEMRA) and CD8+ T cells IFN-γ+, which could hypothetically migrate in the brain parenchyma inducing White Matter alterations. The present study has been developed to evaluate by flow cytometry the immune phenotype of the peripheral blood cells in patients with Schizophrenia and Bipolar Disorder. A flow cytometry analysis has been performed on peripheral blood for the study of T helper and T follicular helper cells and for the evaluation of the NK subpopulations. Then the results have been analysed with manual gating strategy and unsupervised algorithms. The study of NK cells has revealed an important decrease of the immuno-modulatory CD56bright CD16dim neg cells in the peripheral blood of patients, but also an important expression in more and less mature NK cells of CD85j and NKG2C that could be indicative not only of an inflammatory process but also of a previous antigenic stimulation of the immune response, as by Cytomegalovirus. The increase in HLA-DR in CD56bright CD16 dim neg cells of patients has supported the inflammatory hypothesis. Moreover, the analysis of CD4+ T cells has shown the increase in pro-inflammatory cells Th17.1 and the decrease in Th22 in the peripheral blood of patients and the increased expression of CD161 marker among T follicular helper cells. At the same time, it has revealed the increase in patients of Central Memory CD4+ and CD8+ T cells that could be coupled with the reduction of circulating Effector Memory T cells. The results could support the hypothesis of a migration of NK and T populations to the brain parenchyma of patients and the development of inflammation.
La psicosi è una condizione psichiatrica che ha una prevalenza globale importante e rappresenta un serio problema sanitario, specialmente per la sua incidenza in persone giovani ed il rischio di suicidio che determina. Le sue cause possono essere genetiche o ambientali, ma è stato ipotizzato il coinvolgimento di un processo infiammatorio nel cervello in grado di indurre i sintomi della psicosi. Per i pazienti con schizofrenia e disturbo bipolare, è stato evidenziato nel sangue periferico l’incremento delle citochine pro-infiammatorie, l’aumento dei linfociti T e Natural Killer circolanti e l’alterata permeabilità della barriera emato-encefalica. Inoltre, studi precedenti effettuati sul sangue periferico e sulle sezioni di cervello post-mortem di pazienti con disturbo bipolare di tipo I hanno mostrato un importante riduzione nel sangue periferico di linfociti T della memoria effettrice (TEM), linfociti T di memoria terminalmente differenziati (TEMRA) e linfociti T CD8+ IFN- γ+, che potrebbero migrare ipoteticamente nel parenchima cerebrale inducendo delle alterazioni nella materia bianca. Il seguente studio è stato sviluppato per valutare in citometria a flusso il fenotipo immunologico delle cellule nel sangue periferico in pazienti con schizofrenia e disturbo bipolare. Sono stati analizzati grazie alla tecnica della citometria a flusso i linfociti T helper, T helper follicolari e Natural Killer. I risultati sono stati poi analizzati con le strategie di gating manuale ed algoritmi di tipo “unsupervised”. Lo studio dei linfociti Natural Killer ha rivelato un importante riduzione della sottopopolazione CD56br CD16dim/neg nel sangue periferico dei pazienti con psicosi, ma anche l’espressione in NK meno mature o più mature di CD85j e NKG2C che potrebbero essere indicativi non solo di un processo infiammatorio ma anche di una precedente stimolazione della risposta immunitaria a partire da un antigene, come nel caso del Citomegalovirus. L’aumento di HLA-DR nella sottopopolazione NK CD56br CD16dim/neg ha supportato l’ipotesi di un processo infiammatorio. Inoltre, l’analisi dei linfociti T CD4+ ha mostrato un incremento delle cellule pro-infiammatorie Th17.1 e la riduzione delle Th22 nel sangue periferico dei pazienti, insieme all’aumento di una sottopopolazione di T helper follicolari che esprime livelli significativi di CD161. Allo stesso tempo, è stato rilevato l’incremento dei linfociti T CD4+ e CD8+ della memoria centrale nel sangue periferico dei pazienti, che potrebbe essere legato all’aumento di linfociti T della memoria effettrice. I risultati potrebbero supportare l’ipotesi della migrazione dei linfociti T e NK nel parenchima cerebrale dei pazienti e lo sviluppo di un processo infiammatorio.
Characterisation of circulating T and NK cell subsets in patients with Bipolar Disorder or Schizophrenia through conventional and computerized flow cytometry
URAS, CHIARA ROSA MARIA
2024-04-11
Abstract
Psychosis is a condition of the mind that has an important global prevalence and repre-sents a serious health problem, especially due to its incidence on young people and the risk of suicide for them. Its causes can be genetic and environmental, but it has been hypothesized the involvement of brain inflammation in the determining of the psychotic symptoms. For patients with Schizophrenia and Bipolar Disorder, it has been evidenced in the peripheral blood a higher level of pro-inflammatory cytokines, the increase of the circulating T cells and NK cells and the altered permeability of the Blood-Brain-Barrier. In addition, previous studies on the peripheral blood and post-mortem brain sections of patients with Bipolar Disorder I have shown an important reduction in the peripheral blood of T effector memory cells (TEM), Terminally Differentiated Effector Memory T cells (TEMRA) and CD8+ T cells IFN-γ+, which could hypothetically migrate in the brain parenchyma inducing White Matter alterations. The present study has been developed to evaluate by flow cytometry the immune phenotype of the peripheral blood cells in patients with Schizophrenia and Bipolar Disorder. A flow cytometry analysis has been performed on peripheral blood for the study of T helper and T follicular helper cells and for the evaluation of the NK subpopulations. Then the results have been analysed with manual gating strategy and unsupervised algorithms. The study of NK cells has revealed an important decrease of the immuno-modulatory CD56bright CD16dim neg cells in the peripheral blood of patients, but also an important expression in more and less mature NK cells of CD85j and NKG2C that could be indicative not only of an inflammatory process but also of a previous antigenic stimulation of the immune response, as by Cytomegalovirus. The increase in HLA-DR in CD56bright CD16 dim neg cells of patients has supported the inflammatory hypothesis. Moreover, the analysis of CD4+ T cells has shown the increase in pro-inflammatory cells Th17.1 and the decrease in Th22 in the peripheral blood of patients and the increased expression of CD161 marker among T follicular helper cells. At the same time, it has revealed the increase in patients of Central Memory CD4+ and CD8+ T cells that could be coupled with the reduction of circulating Effector Memory T cells. The results could support the hypothesis of a migration of NK and T populations to the brain parenchyma of patients and the development of inflammation.File | Dimensione | Formato | |
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Descrizione: PhD thesis of Chiara Rosa Maria Uras
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