Author/Authors :
Azadbakht ، Mohammad Department of Biology - Faculty of Science - University of Guilan , Sayadmanesh ، Ali Department of Stem Cell and Developmental Biology - Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology - Academic Center for Education, Culture and Research (ACECR) , Nazer ، Naghme Department of Electrical Engineering - Sharif University of Technology , Ahmadi ، Amirhossein Department of Biology - Faculty of Science - Persian Gulf University , Hemmati ، Sara Department of Stem Cell and Developmental Biology - Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology - Academic Center for Education, Culture and Research (ACECR) , Mohammadzade ، Hoda Department of Electrical Engineering - Sharif University of Technology , Ebrahimi ، Marzieh Department of Stem Cell and Developmental Biology - Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology - Academic Center for Education, Culture and Research (ACECR) , Baharvand ، Hossein Department of Stem Cell and Developmental Biology - Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology - Academic Center for Education, Culture and Research (ACECR) , Khalaj ، Babak Department of Electrical Engineering - Sharif University of Technology , Aghamaali ، Mahmoud Reza Department of Biology - Faculty of Science - University of Guilan , Basiri ، Mohsen Department of Stem Cell and Developmental Biology - Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology - Academic Center for Education, Culture and Research (ACECR)
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.
Keywords :
T cell , PRDM1 , BLIMP1 , CRISPR interference , Memory T cell
