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BioImpacts. 2022;12(4): 337-347.
doi: 10.34172/bi.2021.23522
PMID: 35975204
PMCID: PMC9376159
Scopus ID: 85137404752
  Abstract View: 1009
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Original Research

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

Mohammad Azadbakht 1 ORCID logo, Ali Sayadmanesh 2, Naghme Nazer 3, Amirhossein Ahmadi 4, Sara Hemmati 2,5, Hoda Mohammadzade 3, Marzieh Ebrahimi 2, Hossein Baharvand 2,6, Babak Khalaj 3, Mahmoud Reza Aghamaali 1* ORCID logo, Mohsen Basiri 2* ORCID logo

1 Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran
2 Department of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
3 Department of Electrical Engineering, Sharif University of Technology, Tehran, Iran
4 Department of Biology, Faculty of Science, Persian Gulf University, Bushehr, Iran
5 School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
6 Department of Developmental Biology, University of Science and Culture, Tehran, Iran
*Corresponding Authors: *Corresponding authors: Mohsen Basiri, Email: basiri@royan.org; Mahmoud Reza Aghamaali, Email: aghamaali@guilan.ac.ir, Email: aghamaali@guilan.ac.ir; Email: mohsenbasiri@gmail.com

Abstract

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.
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Submitted: 22 Nov 2020
Revision: 05 Nov 2021
Accepted: 08 Nov 2021
ePublished: 07 Dec 2021
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