Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells
The T-box transcription factors T-bet and Eomesodermin regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is widely expressed in the immune system but was initially identified as the lineage-specifying transcription factor of Th1 CD4+ T cells, where it governs expression of t...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1058267/full |
| _version_ | 1797945186838380544 |
|---|---|
| author | Benedikt Thelen Vincent Schipperges Paulina Knörlein Jonas F. Hummel Frederic Arnold Frederic Arnold Frederic Arnold Laurence Kupferschmid Christoph S. N. Klose Sebastian J. Arnold Sebastian J. Arnold Melanie Boerries Melanie Boerries Yakup Tanriver Yakup Tanriver |
| author_facet | Benedikt Thelen Vincent Schipperges Paulina Knörlein Jonas F. Hummel Frederic Arnold Frederic Arnold Frederic Arnold Laurence Kupferschmid Christoph S. N. Klose Sebastian J. Arnold Sebastian J. Arnold Melanie Boerries Melanie Boerries Yakup Tanriver Yakup Tanriver |
| author_sort | Benedikt Thelen |
| collection | DOAJ |
| description | The T-box transcription factors T-bet and Eomesodermin regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is widely expressed in the immune system but was initially identified as the lineage-specifying transcription factor of Th1 CD4+ T cells, where it governs expression of the signature cytokine IFN- γ and represses alternative cell fates like Th2 and Th17. T-bet’s paralog Eomes is less abundantly expressed and Eomes+ CD4+ T cells are mostly found in the context of persistent antigen exposure, like bone marrow transplantation, chronic infection or inflammation as well as malignant disorders. However, it has remained unresolved whether Eomes executes similar transcriptional activities as T-bet in CD4+ T cells. Here we use a novel genetic approach to show that Eomes expression in CD4+ T cells drives a distinct transcriptional program that shows only partial overlap with T-bet. We found that Eomes is sufficient to induce the expression of the immunoregulatory cytokine IL-10 and, together with T-bet, promotes a cytotoxic effector profile, including Prf1, Gzmb, Gzmk, Nkg7 and Ccl5, while repressing alternative cell fates. Our results demonstrate that Eomes+ CD4+ T cells, which are often found in the context of chronic antigen stimulation, are likely to be a unique CD4+ T cell subset that limits inflammation and immunopathology as well as eliminates antigen-presenting and malignant cells. |
| first_indexed | 2024-04-10T20:50:09Z |
| format | Article |
| id | doaj.art-4c5f1626cfc8418480d9a58bd7d61b97 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T20:50:09Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4c5f1626cfc8418480d9a58bd7d61b972023-01-23T14:50:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.10582671058267Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cellsBenedikt Thelen0Vincent Schipperges1Paulina Knörlein2Jonas F. Hummel3Frederic Arnold4Frederic Arnold5Frederic Arnold6Laurence Kupferschmid7Christoph S. N. Klose8Sebastian J. Arnold9Sebastian J. Arnold10Melanie Boerries11Melanie Boerries12Yakup Tanriver13Yakup Tanriver14Institute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Medical Bioinformatics and Systems Medicine, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, GermanyInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Internal Medicine IV, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, GermanyBerta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, GermanyCIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, GermanyInstitute of Medical Bioinformatics and Systems Medicine, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, GermanyGerman Cancer Consortium (Deutsches Konsortium für Translationale Krebsforschung, DKTK), Partner Site Freiburg, and German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Heidelberg, GermanyInstitute of Medical Microbiology and Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Internal Medicine IV, Faculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, GermanyThe T-box transcription factors T-bet and Eomesodermin regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is widely expressed in the immune system but was initially identified as the lineage-specifying transcription factor of Th1 CD4+ T cells, where it governs expression of the signature cytokine IFN- γ and represses alternative cell fates like Th2 and Th17. T-bet’s paralog Eomes is less abundantly expressed and Eomes+ CD4+ T cells are mostly found in the context of persistent antigen exposure, like bone marrow transplantation, chronic infection or inflammation as well as malignant disorders. However, it has remained unresolved whether Eomes executes similar transcriptional activities as T-bet in CD4+ T cells. Here we use a novel genetic approach to show that Eomes expression in CD4+ T cells drives a distinct transcriptional program that shows only partial overlap with T-bet. We found that Eomes is sufficient to induce the expression of the immunoregulatory cytokine IL-10 and, together with T-bet, promotes a cytotoxic effector profile, including Prf1, Gzmb, Gzmk, Nkg7 and Ccl5, while repressing alternative cell fates. Our results demonstrate that Eomes+ CD4+ T cells, which are often found in the context of chronic antigen stimulation, are likely to be a unique CD4+ T cell subset that limits inflammation and immunopathology as well as eliminates antigen-presenting and malignant cells.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1058267/fullCD4 T cellEomesIL-10Tr1LCMV (lymphocytic choriomeningitis virus)cytotoxcicity |
| spellingShingle | Benedikt Thelen Vincent Schipperges Paulina Knörlein Jonas F. Hummel Frederic Arnold Frederic Arnold Frederic Arnold Laurence Kupferschmid Christoph S. N. Klose Sebastian J. Arnold Sebastian J. Arnold Melanie Boerries Melanie Boerries Yakup Tanriver Yakup Tanriver Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells Frontiers in Immunology CD4 T cell Eomes IL-10 Tr1 LCMV (lymphocytic choriomeningitis virus) cytotoxcicity |
| title | Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells |
| title_full | Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells |
| title_fullStr | Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells |
| title_full_unstemmed | Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells |
| title_short | Eomes is sufficient to regulate IL-10 expression and cytotoxic effector molecules in murine CD4+ T cells |
| title_sort | eomes is sufficient to regulate il 10 expression and cytotoxic effector molecules in murine cd4 t cells |
| topic | CD4 T cell Eomes IL-10 Tr1 LCMV (lymphocytic choriomeningitis virus) cytotoxcicity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1058267/full |
| work_keys_str_mv | AT benediktthelen eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT vincentschipperges eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT paulinaknorlein eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT jonasfhummel eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT fredericarnold eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT fredericarnold eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT fredericarnold eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT laurencekupferschmid eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT christophsnklose eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT sebastianjarnold eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT sebastianjarnold eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT melanieboerries eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT melanieboerries eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT yakuptanriver eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells AT yakuptanriver eomesissufficienttoregulateil10expressionandcytotoxiceffectormoleculesinmurinecd4tcells |