Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations
DNA damage occurs constantly in every cell triggered by endogenous processes of replication and metabolism, and external influences such as ionizing radiation and intercalating chemicals. Large sets of proteins are involved in sensing, stabilizing and repairing this damage including control of cell...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.739675/full |
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| author | Kerstin Felgentreff Catharina Schuetz Ulrich Baumann Christian Klemann Dorothee Viemann Simona Ursu Eva-Maria Jacobsen Klaus-Michael Debatin Ansgar Schulz Manfred Hoenig Manfred Hoenig Klaus Schwarz Klaus Schwarz |
| author_facet | Kerstin Felgentreff Catharina Schuetz Ulrich Baumann Christian Klemann Dorothee Viemann Simona Ursu Eva-Maria Jacobsen Klaus-Michael Debatin Ansgar Schulz Manfred Hoenig Manfred Hoenig Klaus Schwarz Klaus Schwarz |
| author_sort | Kerstin Felgentreff |
| collection | DOAJ |
| description | DNA damage occurs constantly in every cell triggered by endogenous processes of replication and metabolism, and external influences such as ionizing radiation and intercalating chemicals. Large sets of proteins are involved in sensing, stabilizing and repairing this damage including control of cell cycle and proliferation. Some of these factors are phosphorylated upon activation and can be used as biomarkers of DNA damage response (DDR) by flow and mass cytometry. Differential survival rates of lymphocyte subsets in response to DNA damage are well established, characterizing NK cells as most resistant and B cells as most sensitive to DNA damage. We investigated DDR to low dose gamma radiation (2Gy) in peripheral blood lymphocytes of 26 healthy donors and 3 patients with ataxia telangiectasia (AT) using mass cytometry. γH2AX, p-CHK2, p-ATM and p53 were analyzed as specific DDR biomarkers for functional readouts of DNA repair efficiency in combination with cell cycle and T, B and NK cell populations characterized by 20 surface markers. We identified significant differences in DDR among lymphocyte populations in healthy individuals. Whereas CD56+CD16+ NK cells showed a strong γH2AX response to low dose ionizing radiation, a reduced response rate could be observed in CD19+CD20+ B cells that was associated with reduced survival. Interestingly, γH2AX induction level correlated inversely with ATM-dependent p-CHK2 and p53 responses. Differential DDR could be further noticed in naïve compared to memory T and B cell subsets, characterized by reduced γH2AX, but increased p53 induction in naïve T cells. In contrast, DDR was abrogated in all lymphocyte populations of AT patients. Our results demonstrate differential DDR capacities in lymphocyte subsets that depend on maturation and correlate inversely with DNA damage-related survival. Importantly, DDR analysis of peripheral blood cells for diagnostic purposes should be stratified to lymphocyte subsets. |
| first_indexed | 2024-12-16T23:53:37Z |
| format | Article |
| id | doaj.art-89876b1571e748649cdd3460c28cd32c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-16T23:53:37Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-89876b1571e748649cdd3460c28cd32c2022-12-21T22:11:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.739675739675Differential DNA Damage Response of Peripheral Blood Lymphocyte PopulationsKerstin Felgentreff0Catharina Schuetz1Ulrich Baumann2Christian Klemann3Dorothee Viemann4Simona Ursu5Eva-Maria Jacobsen6Klaus-Michael Debatin7Ansgar Schulz8Manfred Hoenig9Manfred Hoenig10Klaus Schwarz11Klaus Schwarz12Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyDepartment of Pediatrics, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, GermanyDepartment of Pediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, GermanyDepartment of Pediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, GermanyDepartment of Pediatric Pulmonology, Allergy and Neonatology, Hannover Medical School, Hannover, GermanyCore Facility Cytometry, Ulm University Medical Faculty, Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyCore Facility Cytometry, Ulm University Medical Faculty, Ulm, GermanyInstitute for Transfusion Medicine, University Ulm, Ulm, GermanyThe Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Service Baden-Wuerttemberg - Hessen, Ulm, GermanyDNA damage occurs constantly in every cell triggered by endogenous processes of replication and metabolism, and external influences such as ionizing radiation and intercalating chemicals. Large sets of proteins are involved in sensing, stabilizing and repairing this damage including control of cell cycle and proliferation. Some of these factors are phosphorylated upon activation and can be used as biomarkers of DNA damage response (DDR) by flow and mass cytometry. Differential survival rates of lymphocyte subsets in response to DNA damage are well established, characterizing NK cells as most resistant and B cells as most sensitive to DNA damage. We investigated DDR to low dose gamma radiation (2Gy) in peripheral blood lymphocytes of 26 healthy donors and 3 patients with ataxia telangiectasia (AT) using mass cytometry. γH2AX, p-CHK2, p-ATM and p53 were analyzed as specific DDR biomarkers for functional readouts of DNA repair efficiency in combination with cell cycle and T, B and NK cell populations characterized by 20 surface markers. We identified significant differences in DDR among lymphocyte populations in healthy individuals. Whereas CD56+CD16+ NK cells showed a strong γH2AX response to low dose ionizing radiation, a reduced response rate could be observed in CD19+CD20+ B cells that was associated with reduced survival. Interestingly, γH2AX induction level correlated inversely with ATM-dependent p-CHK2 and p53 responses. Differential DDR could be further noticed in naïve compared to memory T and B cell subsets, characterized by reduced γH2AX, but increased p53 induction in naïve T cells. In contrast, DDR was abrogated in all lymphocyte populations of AT patients. Our results demonstrate differential DDR capacities in lymphocyte subsets that depend on maturation and correlate inversely with DNA damage-related survival. Importantly, DDR analysis of peripheral blood cells for diagnostic purposes should be stratified to lymphocyte subsets.https://www.frontiersin.org/articles/10.3389/fimmu.2021.739675/fullDNA damage responseperipheral blood lymphocyte subsetsmass cytometryataxia telangiectasiacell cycle |
| spellingShingle | Kerstin Felgentreff Catharina Schuetz Ulrich Baumann Christian Klemann Dorothee Viemann Simona Ursu Eva-Maria Jacobsen Klaus-Michael Debatin Ansgar Schulz Manfred Hoenig Manfred Hoenig Klaus Schwarz Klaus Schwarz Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations Frontiers in Immunology DNA damage response peripheral blood lymphocyte subsets mass cytometry ataxia telangiectasia cell cycle |
| title | Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations |
| title_full | Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations |
| title_fullStr | Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations |
| title_full_unstemmed | Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations |
| title_short | Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations |
| title_sort | differential dna damage response of peripheral blood lymphocyte populations |
| topic | DNA damage response peripheral blood lymphocyte subsets mass cytometry ataxia telangiectasia cell cycle |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.739675/full |
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