Immune Phenotypic Characterization of a TRAIL-Knockout Mouse
The TNF-superfamily member TRAIL is known to mediate selective apoptosis in tumor cells suggesting this protein as a potential antitumor drug target. However, initial successful pr-clinical results could not be translated into the clinic. Reasons for the ineffectiveness of TRAIL-targeting in tumor t...
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| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/5/1475 |
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| author | Ani K. Stoyanova Arne Sattler Elisabeth M. Hahn Nina A. Hering Marco Arndt Johannes Christian Lauscher Fiona Speichinger-Hillenberg Katja Kotsch Ann-Kathrin Berg Katharina Beyer |
| author_facet | Ani K. Stoyanova Arne Sattler Elisabeth M. Hahn Nina A. Hering Marco Arndt Johannes Christian Lauscher Fiona Speichinger-Hillenberg Katja Kotsch Ann-Kathrin Berg Katharina Beyer |
| author_sort | Ani K. Stoyanova |
| collection | DOAJ |
| description | The TNF-superfamily member TRAIL is known to mediate selective apoptosis in tumor cells suggesting this protein as a potential antitumor drug target. However, initial successful pr-clinical results could not be translated into the clinic. Reasons for the ineffectiveness of TRAIL-targeting in tumor therapies could include acquired TRAIL resistance. A tumor cell acquires TRAIL resistance, for example, by upregulation of antiapoptotic proteins. In addition, TRAIL can also influence the immune system and thus, tumor growth. We were able to show in our previous work that TRAIL<sup>−/−</sup> mice show improved survival in a mouse model of pancreatic carcinoma. Therefore, in this study we aimed to immunologically characterize the TRAIL<sup>−/−</sup> mice. We observed no significant differences in the distribution of CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup> T-cells, Tregs, and central memory CD4<sup>+</sup> and CD8<sup>+</sup> cells. However, we provide evidence for relevant differences in the distribution of effector memory T-cells and CD8<sup>+</sup>CD122<sup>+</sup> cells but also in dendritic cells. Our findings suggest that T-lymphocytes of TRAIL<sup>−/−</sup> mice proliferate at a lower rate, and that the administration of recombinant TRAIL significantly increases their proliferation, while regulatory T-cells (Tregs) from TRAIL<sup>−/−</sup> mice are less suppressive. Regarding the dendritic cells, we found more type-2 conventional dendritic cells (DC2s) in the TRAIL<sup>−/−</sup> mice. For the first time (to the best of our knowledge), we provide a comprehensive characterization of the immunological landscape of TRAIL-deficient mice. This will establish an experimental basis for future investigations of TRAIL-mediated immunology. |
| first_indexed | 2024-03-11T07:29:23Z |
| format | Article |
| id | doaj.art-09577f44f5ac40999965b42f90a4eac2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T07:29:23Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-09577f44f5ac40999965b42f90a4eac22023-11-17T07:24:36ZengMDPI AGCancers2072-66942023-02-01155147510.3390/cancers15051475Immune Phenotypic Characterization of a TRAIL-Knockout MouseAni K. Stoyanova0Arne Sattler1Elisabeth M. Hahn2Nina A. Hering3Marco Arndt4Johannes Christian Lauscher5Fiona Speichinger-Hillenberg6Katja Kotsch7Ann-Kathrin Berg8Katharina Beyer9Department of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyDepartment of General, Visceral and Vascular Surgery, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, GermanyThe TNF-superfamily member TRAIL is known to mediate selective apoptosis in tumor cells suggesting this protein as a potential antitumor drug target. However, initial successful pr-clinical results could not be translated into the clinic. Reasons for the ineffectiveness of TRAIL-targeting in tumor therapies could include acquired TRAIL resistance. A tumor cell acquires TRAIL resistance, for example, by upregulation of antiapoptotic proteins. In addition, TRAIL can also influence the immune system and thus, tumor growth. We were able to show in our previous work that TRAIL<sup>−/−</sup> mice show improved survival in a mouse model of pancreatic carcinoma. Therefore, in this study we aimed to immunologically characterize the TRAIL<sup>−/−</sup> mice. We observed no significant differences in the distribution of CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup> T-cells, Tregs, and central memory CD4<sup>+</sup> and CD8<sup>+</sup> cells. However, we provide evidence for relevant differences in the distribution of effector memory T-cells and CD8<sup>+</sup>CD122<sup>+</sup> cells but also in dendritic cells. Our findings suggest that T-lymphocytes of TRAIL<sup>−/−</sup> mice proliferate at a lower rate, and that the administration of recombinant TRAIL significantly increases their proliferation, while regulatory T-cells (Tregs) from TRAIL<sup>−/−</sup> mice are less suppressive. Regarding the dendritic cells, we found more type-2 conventional dendritic cells (DC2s) in the TRAIL<sup>−/−</sup> mice. For the first time (to the best of our knowledge), we provide a comprehensive characterization of the immunological landscape of TRAIL-deficient mice. This will establish an experimental basis for future investigations of TRAIL-mediated immunology.https://www.mdpi.com/2072-6694/15/5/1475TRAIL: immunological phenotypelymphocytesdendritic cellsknockout mouse |
| spellingShingle | Ani K. Stoyanova Arne Sattler Elisabeth M. Hahn Nina A. Hering Marco Arndt Johannes Christian Lauscher Fiona Speichinger-Hillenberg Katja Kotsch Ann-Kathrin Berg Katharina Beyer Immune Phenotypic Characterization of a TRAIL-Knockout Mouse Cancers TRAIL: immunological phenotype lymphocytes dendritic cells knockout mouse |
| title | Immune Phenotypic Characterization of a TRAIL-Knockout Mouse |
| title_full | Immune Phenotypic Characterization of a TRAIL-Knockout Mouse |
| title_fullStr | Immune Phenotypic Characterization of a TRAIL-Knockout Mouse |
| title_full_unstemmed | Immune Phenotypic Characterization of a TRAIL-Knockout Mouse |
| title_short | Immune Phenotypic Characterization of a TRAIL-Knockout Mouse |
| title_sort | immune phenotypic characterization of a trail knockout mouse |
| topic | TRAIL: immunological phenotype lymphocytes dendritic cells knockout mouse |
| url | https://www.mdpi.com/2072-6694/15/5/1475 |
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