PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome
T cell hyporesponsiveness is crucial for the functional immune system and prevents the damage induced by alloreactive T cells in autoimmune pathology and transplantation. Here, we found low expression of PRDM1 in T cells from donor and recipients both related to the occurrence of acute graft-versus-...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.879501/full |
| _version_ | 1818009545367093248 |
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| author | Huidong Guo Ming Wang Bixia Wang Liping Guo Yifei Cheng Zhidong Wang Yu-Qian Sun Yu Wang Ying-Jun Chang Xiao-Jun Huang Xiao-Jun Huang Xiao-Jun Huang Xiao-Jun Huang |
| author_facet | Huidong Guo Ming Wang Bixia Wang Liping Guo Yifei Cheng Zhidong Wang Yu-Qian Sun Yu Wang Ying-Jun Chang Xiao-Jun Huang Xiao-Jun Huang Xiao-Jun Huang Xiao-Jun Huang |
| author_sort | Huidong Guo |
| collection | DOAJ |
| description | T cell hyporesponsiveness is crucial for the functional immune system and prevents the damage induced by alloreactive T cells in autoimmune pathology and transplantation. Here, we found low expression of PRDM1 in T cells from donor and recipients both related to the occurrence of acute graft-versus-host disease (aGVHD). Our systematic multiomics analysis found that the transcription factor PRDM1 acts as a master regulator during inducing human primary T cell hyporesponsiveness. PRDM1-overexpression in primary T cells expanded Treg cell subset and increased the expression level of FOXP3, while decreased expression had the opposite effects. Moreover, the binding motifs of key T cell function regulators, such as FOS, JUN and AP-1, were enriched in PRDM1 binding sites and that PRDM1 altered the chromatin accessibility of these regions. Multiomics analysis showed that PRDM1 directly upregulated T cell inhibitory genes such as KLF2 and KLRD1 and downregulated the T cell activation gene IL2, indicating that PRDM1 could promote a tolerant transcriptional profile. Further analysis showed that PRDM1 upregulated FOXP3 expression level directly by binding to FOXP3 upstream enhancer region and indirectly by upregulating KLF2. These results indicated that PRDM1 is sufficient for inducing human primary T cell hyporesponsiveness by transcriptomic and epigenetic manners. |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T05:44:06Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-a1217ec77e9c4f3a86525878a28dc96b2022-12-22T02:09:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.879501879501PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and EpigenomeHuidong Guo0Ming Wang1Bixia Wang2Liping Guo3Yifei Cheng4Zhidong Wang5Yu-Qian Sun6Yu Wang7Ying-Jun Chang8Xiao-Jun Huang9Xiao-Jun Huang10Xiao-Jun Huang11Xiao-Jun Huang12Peking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, ChinaNanfang Hospital, Southern Medical University, Guangzhou, ChinaNanfang Hospital, Southern Medical University, Guangzhou, ChinaPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, ChinaPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, ChinaPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, ChinaPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, ChinaPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, ChinaPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, ChinaPeking University People’s Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, ChinaNanfang Hospital, Southern Medical University, Guangzhou, ChinaPeking-Tsinghua Center for Life Sciences, School of Life Sciences, Peking University, Beijing, ChinaResearch Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies (2019RU029), Chinese Academy of Medical Sciences, Beijing, ChinaT cell hyporesponsiveness is crucial for the functional immune system and prevents the damage induced by alloreactive T cells in autoimmune pathology and transplantation. Here, we found low expression of PRDM1 in T cells from donor and recipients both related to the occurrence of acute graft-versus-host disease (aGVHD). Our systematic multiomics analysis found that the transcription factor PRDM1 acts as a master regulator during inducing human primary T cell hyporesponsiveness. PRDM1-overexpression in primary T cells expanded Treg cell subset and increased the expression level of FOXP3, while decreased expression had the opposite effects. Moreover, the binding motifs of key T cell function regulators, such as FOS, JUN and AP-1, were enriched in PRDM1 binding sites and that PRDM1 altered the chromatin accessibility of these regions. Multiomics analysis showed that PRDM1 directly upregulated T cell inhibitory genes such as KLF2 and KLRD1 and downregulated the T cell activation gene IL2, indicating that PRDM1 could promote a tolerant transcriptional profile. Further analysis showed that PRDM1 upregulated FOXP3 expression level directly by binding to FOXP3 upstream enhancer region and indirectly by upregulating KLF2. These results indicated that PRDM1 is sufficient for inducing human primary T cell hyporesponsiveness by transcriptomic and epigenetic manners.https://www.frontiersin.org/articles/10.3389/fimmu.2022.879501/fullPRDM1multiomicsT cell hyporesponsivenessHSCTGvHD |
| spellingShingle | Huidong Guo Ming Wang Bixia Wang Liping Guo Yifei Cheng Zhidong Wang Yu-Qian Sun Yu Wang Ying-Jun Chang Xiao-Jun Huang Xiao-Jun Huang Xiao-Jun Huang Xiao-Jun Huang PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome Frontiers in Immunology PRDM1 multiomics T cell hyporesponsiveness HSCT GvHD |
| title | PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome |
| title_full | PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome |
| title_fullStr | PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome |
| title_full_unstemmed | PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome |
| title_short | PRDM1 Drives Human Primary T Cell Hyporesponsiveness by Altering the T Cell Transcriptome and Epigenome |
| title_sort | prdm1 drives human primary t cell hyporesponsiveness by altering the t cell transcriptome and epigenome |
| topic | PRDM1 multiomics T cell hyporesponsiveness HSCT GvHD |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.879501/full |
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