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T regulatory cells as a potential therapeutic target in psychosis? Current challenges and future perspectives

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Corsi-Zuelli, Fabiana ; Deakin, Bill ; Lima, Mikhael Haruo Fernandes de ; Qureshi, Omar ; Barnes, Nicholas M. ; Upthegrove, Rachel ; Louzada-Junior, Paulo ; Del-Ben, Cristina Marta
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: BRAIN, BEHAVIOR, & IMMUNITY - HEALTH; v. 17, p. 14-pg., 2021-11-01.

Many studies have reported that patients with psychosis, even before drug treatment, have mildly raised levels of blood cytokines relative to healthy controls. In contrast, there is a remarkable scarcity of studies investigating the cellular basis of immune function and cytokine changes in psychosis. The few flow-cytometry studies have been limited to counting the proportion of the major classes of monocyte and lymphocytes without distinguishing their pro- and anti-inflammatory subsets. Moreover, most of the investigations are cross-sectional and conducted with patients on long-term medication. These features make it difficult to eliminate confounding of illness-related changes by lifestyle factors, disease duration, and long exposure to antipsychotics. This article focuses on regulatory T cells (Tregs), cornerstone immune cells that regulate innate and adaptive immune forces and neuroimmune interactions between astrocytes and microglia. Tregs are also implicated in cardio-metabolic disorders that are common comorbidities of psychosis. We have recently proposed that Tregs are hypofunctional ('h-Tregs') in psychosis driven by our clinical findings and other independent research. Our h-Treg-glial imbalance hypothesis offers a new account for the co-occurrence of systemic immune dysregulation and mechanisms of psychosis development. This article extends our recent review, the h-Treg hypothesis, to cover new discoveries on Treg-based therapies from pre-clinical findings and their clinical implications. We provide a detailed characterisation of Treg studies in psychosis, identifying important methodological limitations and perspectives for scientific innovation. The outcomes presented in this article reaffirms our proposed h-Treg state in psychosis and reveals emerging preclinical research suggesting the potential benefit of Treg-enhancing therapies. There is a clear need for longitudinal studies conducted with drug-naive or minimally treated patients using more sophisticated techniques of flow-cytometry, CyTOF expression markers, and in vitro co-culture assays to formally test the suppressive capacity of Tregs. Investment in Treg research offers major potential benefits in targeting emerging immunomodulatory treatment modalities on person-specific immune dysregulations. (AU)

Processo FAPESP: 12/05178-0 - Esquizofrenia e outros transtornos psicóticos: determinantes sociais e biológicos
Beneficiário:Paulo Rossi Menezes
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
Beneficiário:Fernando de Queiroz Cunha
Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 20/02642-3 - Caracterização da subpopulação de células T reguladoras TIGIT+ na resposta à terapia com drogas anti-reumátidas modificadoras de doença em pacientes com Artrite Reumatoide
Beneficiário:Mikhael Haruo Fernandes de Lima
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
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
Processo FAPESP: 21/07448-3 - Imunofenotipagem de pacientes com psicose imunologicamente ativos e o papel da interleucina-6
Beneficiário:Fabiana Maria das Graças Corsi Zuelli
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado