CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells
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 a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Tabriz University of Medical Sciences
2022-07-01
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| Series: | BioImpacts |
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| Online Access: | https://bi.tbzmed.ac.ir/PDF/bi-12-337.pdf |
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| author | Mohammad Azadbakht Ali Sayadmanesh Naghme Nazer Amirhossein Ahmadi Sara Hemmati Hoda Mohammadzade Marzieh Ebrahimi Hossein Baharvand Babak Khalaj Mahmoud Reza Aghamaali Mohsen Basiri |
| author_facet | Mohammad Azadbakht Ali Sayadmanesh Naghme Nazer Amirhossein Ahmadi Sara Hemmati Hoda Mohammadzade Marzieh Ebrahimi Hossein Baharvand Babak Khalaj Mahmoud Reza Aghamaali Mohsen Basiri |
| author_sort | Mohammad Azadbakht |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:28:45Z |
| format | Article |
| id | doaj.art-50351407847848979e396966d34f5c7b |
| institution | Directory Open Access Journal |
| issn | 2228-5660 2228-5652 |
| language | English |
| last_indexed | 2024-04-13T15:28:45Z |
| publishDate | 2022-07-01 |
| publisher | Tabriz University of Medical Sciences |
| record_format | Article |
| series | BioImpacts |
| spelling | doaj.art-50351407847848979e396966d34f5c7b2022-12-22T02:41:26ZengTabriz University of Medical SciencesBioImpacts2228-56602228-56522022-07-0112433734710.34172/bi.2021.23522bi-23522CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cellsMohammad Azadbakht0Ali Sayadmanesh1Naghme Nazer2Amirhossein Ahmadi3Sara Hemmati4Hoda Mohammadzade5Marzieh Ebrahimi6Hossein Baharvand7Babak Khalaj8Mahmoud Reza Aghamaali9Mohsen Basiri10Department of Biology, Faculty of Science, University of Guilan, Rasht, IranDepartment of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Electrical Engineering, Sharif University of Technology, Tehran, IranDepartment of Biology, Faculty of Science, Persian Gulf University, Bushehr, IranDepartment of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Electrical Engineering, Sharif University of Technology, Tehran, IranDepartment of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Electrical Engineering, Sharif University of Technology, Tehran, IranDepartment of Biology, Faculty of Science, University of Guilan, Rasht, IranDepartment of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranIntroduction: 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.https://bi.tbzmed.ac.ir/PDF/bi-12-337.pdft cellprdm1blimp1crispr interferencememory t cell |
| spellingShingle | Mohammad Azadbakht Ali Sayadmanesh Naghme Nazer Amirhossein Ahmadi Sara Hemmati Hoda Mohammadzade Marzieh Ebrahimi Hossein Baharvand Babak Khalaj Mahmoud Reza Aghamaali Mohsen Basiri CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells BioImpacts t cell prdm1 blimp1 crispr interference memory t cell |
| title | CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells |
| title_full | CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells |
| title_fullStr | CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells |
| title_full_unstemmed | CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells |
| title_short | CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells |
| title_sort | crispri mediated knock down of prdm1 blimp1 programs central memory differentiation in ex vivo expanded human t cells |
| topic | t cell prdm1 blimp1 crispr interference memory t cell |
| url | https://bi.tbzmed.ac.ir/PDF/bi-12-337.pdf |
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