Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells
GM-CSF produced by autoreactive CD4-positive T helper cells is involved in the pathogenesis of autoimmune diseases, such as multiple sclerosis. However, the molecular regulators that establish and maintain the features of GM-CSF-positive CD4 T cells are unknown. In order to identify these regulators...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/8880585 |
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| _version_ | 1832561131968790528 |
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| author | Szabolcs Éliás Angelika Schmidt David Gomez-Cabrero Jesper Tegnér |
| author_facet | Szabolcs Éliás Angelika Schmidt David Gomez-Cabrero Jesper Tegnér |
| author_sort | Szabolcs Éliás |
| collection | DOAJ |
| description | GM-CSF produced by autoreactive CD4-positive T helper cells is involved in the pathogenesis of autoimmune diseases, such as multiple sclerosis. However, the molecular regulators that establish and maintain the features of GM-CSF-positive CD4 T cells are unknown. In order to identify these regulators, we isolated human GM-CSF-producing CD4 T cells from human peripheral blood by using a cytokine capture assay. We compared these cells to the corresponding GM-CSF-negative fraction, and furthermore, we studied naïve CD4 T cells, memory CD4 T cells, and bulk CD4 T cells from the same individuals as additional control cell populations. As a result, we provide a rich resource of integrated chromatin accessibility (ATAC-seq) and transcriptome (RNA-seq) data from these primary human CD4 T cell subsets and we show that the identified signatures are associated with human autoimmune diseases, especially multiple sclerosis. By combining information about mRNA expression, DNA accessibility, and predicted transcription factor binding, we reconstructed directed gene regulatory networks connecting transcription factors to their targets, which comprise putative key regulators of human GM-CSF-positive CD4 T cells as well as memory CD4 T cells. Our results suggest potential therapeutic targets to be investigated in the future in human autoimmune disease. |
| format | Article |
| id | doaj-art-1c4d12510e5b4deab3c78d3fb5811821 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-1c4d12510e5b4deab3c78d3fb58118212025-02-03T01:25:49ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/88805858880585Gene Regulatory Network of Human GM-CSF-Secreting T Helper CellsSzabolcs Éliás0Angelika Schmidt1David Gomez-Cabrero2Jesper Tegnér3Unit of Computational Medicine, Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital & Science for Life Laboratory, 17176 Solna, Stockholm, SwedenUnit of Computational Medicine, Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital & Science for Life Laboratory, 17176 Solna, Stockholm, SwedenUnit of Computational Medicine, Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital & Science for Life Laboratory, 17176 Solna, Stockholm, SwedenUnit of Computational Medicine, Center for Molecular Medicine, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital & Science for Life Laboratory, 17176 Solna, Stockholm, SwedenGM-CSF produced by autoreactive CD4-positive T helper cells is involved in the pathogenesis of autoimmune diseases, such as multiple sclerosis. However, the molecular regulators that establish and maintain the features of GM-CSF-positive CD4 T cells are unknown. In order to identify these regulators, we isolated human GM-CSF-producing CD4 T cells from human peripheral blood by using a cytokine capture assay. We compared these cells to the corresponding GM-CSF-negative fraction, and furthermore, we studied naïve CD4 T cells, memory CD4 T cells, and bulk CD4 T cells from the same individuals as additional control cell populations. As a result, we provide a rich resource of integrated chromatin accessibility (ATAC-seq) and transcriptome (RNA-seq) data from these primary human CD4 T cell subsets and we show that the identified signatures are associated with human autoimmune diseases, especially multiple sclerosis. By combining information about mRNA expression, DNA accessibility, and predicted transcription factor binding, we reconstructed directed gene regulatory networks connecting transcription factors to their targets, which comprise putative key regulators of human GM-CSF-positive CD4 T cells as well as memory CD4 T cells. Our results suggest potential therapeutic targets to be investigated in the future in human autoimmune disease.http://dx.doi.org/10.1155/2021/8880585 |
| spellingShingle | Szabolcs Éliás Angelika Schmidt David Gomez-Cabrero Jesper Tegnér Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells Journal of Immunology Research |
| title | Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells |
| title_full | Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells |
| title_fullStr | Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells |
| title_full_unstemmed | Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells |
| title_short | Gene Regulatory Network of Human GM-CSF-Secreting T Helper Cells |
| title_sort | gene regulatory network of human gm csf secreting t helper cells |
| url | http://dx.doi.org/10.1155/2021/8880585 |
| work_keys_str_mv | AT szabolcselias generegulatorynetworkofhumangmcsfsecretingthelpercells AT angelikaschmidt generegulatorynetworkofhumangmcsfsecretingthelpercells AT davidgomezcabrero generegulatorynetworkofhumangmcsfsecretingthelpercells AT jespertegner generegulatorynetworkofhumangmcsfsecretingthelpercells |