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CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells

[Image: see text] Introduction: B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (PRDM1), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. Methods: I...

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Detalles Bibliográficos
Autores principales: Azadbakht, Mohammad, Sayadmanesh, Ali, Nazer, Naghme, Ahmadi, Amirhossein, Hemmati, Sara, Mohammadzade, Hoda, Ebrahimi, Marzieh, Baharvand, Hossein, Khalaj, Babak, Aghamaali, Mahmoud Reza, Basiri, Mohsen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Tabriz University of Medical Sciences (TUOMS Publishing Group) 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9376159/
https://www.ncbi.nlm.nih.gov/pubmed/35975204
http://dx.doi.org/10.34172/bi.2021.23522
Descripción
Sumario:[Image: see text] Introduction: B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (PRDM1), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. Methods: In this study, we aimed to determine the role of transcription factor BLIMP1 in human T cell differentiation. Specifically, we investigated the role of BLIMP1 in memory differentiation and exhaustion of human T cells. We used CRISPR interference (CRISPRi) to knock-down BLIMP1 and investigated the differential expressions of T cell memory and exhaustion markers in BLIMP1-deficient T cells in comparison with BLIMP1-sufficient ex vivo expanded human T cells. Results: BLIMP1-deficiency caused an increase in central memory (CM) T cells and a decrease in effector memory (EM) T cells. There was a decrease in the amount of TIM3 exhaustion marker expression in BLIMP1-deficient T cells; however, there was an increase in PD1 exhaustion marker expression in BLIMP1-deficient T cells compared with BLIMP1-sufficient T cells. Conclusion: Our study provides the first functional evidence of the impact of BLIMP1 on the regulation of human T cell memory and exhaustion phenotype. These findings suggest that BLIMP1 may be a promising target to improve the immune response in adoptive T cell therapy settings.