Impaired regulatory T cell control of astroglial overdrive and microglial pruning in schizophrenia

Autor(es)

Corsi-Zuelli, Fabiana ^[1] ; Deakin, Bill ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Div Psychiat, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Biol Med & Hlth, Div Neurosci & Expt Psychol, Sch Biol Sci, Manchester M13 9PT, Lancs - England

• Tipo de documento: Artigo Científico
• Fonte: NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS; v. 125, p. 637-653, JUN 2021.
• Citações Web of Science: 0

Resumo

It is widely held that schizophrenia involves an active process of peripheral inflammation that induces or reflects brain inflammation with activation of microglia, the brain?s resident immune cells. However, recent in vivo radioligand binding studies and large-scale transcriptomics in post-mortem brain report reduced markers of microglial inflammation. The findings suggest a contrary hypothesis; that microglia are diverted into their noninflammatory synaptic remodelling phenotype that interferes with neurodevelopment and perhaps contributes to the relapsing nature of schizophrenia. Recent discoveries on the regulatory interactions between micro- and astroglial cells and immune regulatory T cells (Tregs) cohere with clinical omics data to suggest that: i) disinhibited astrocytes mediate the shift in microglial phenotype via the production of transforming growth factorbeta, which also contributes to the disturbances of dopamine and GABA function in schizophrenia, and ii) systemically impaired functioning of Treg cells contributes to the dysregulation of glial function, the low-grade peripheral inflammation, and the hitherto unexplained predisposition to auto-immunity and reduced lifeexpectancy in schizophrenia, including greater COVID-19 mortality. (AU)

• Processo FAPESP: 19/13229-2 - Perfil inflamatório na população geral: evidência dimensional transdiagnóstica no contexto do continuum das psicoses
• Beneficiário: Fabiana Maria das Graças Corsi Zuelli
• Modalidade de apoio: Bolsas no Brasil - Doutorado