Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 Infection
Antonia Becker,1 Karoline Röhrich,1 Amanda Leske,1 Ulrike Heinicke,1 Tilo Knape,2 Aimo Kannt,2,3 Verena Trümper,4 Kai Sohn,5 Annett Wilken-Schmitz,1 Holger Neb,1 Elisabeth H Adam,1 Volker Laux,2 Michael J Parnham,2 Valerie Onasch,4 Andreas Weigert,4 Kai Zacharowski,1,2 Andreas von Knethen1 1Goethe U...
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Dove Medical Press
2024-11-01
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| Series: | ImmunoTargets and Therapy |
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| author | Becker A Röhrich K Leske A Heinicke U Knape T Kannt A Trümper V Sohn K Wilken-Schmitz A Neb H Adam EH Laux V Parnham MJ Onasch V Weigert A Zacharowski K von Knethen A |
| author_facet | Becker A Röhrich K Leske A Heinicke U Knape T Kannt A Trümper V Sohn K Wilken-Schmitz A Neb H Adam EH Laux V Parnham MJ Onasch V Weigert A Zacharowski K von Knethen A |
| author_sort | Becker A |
| collection | DOAJ |
| description | Antonia Becker,1 Karoline Röhrich,1 Amanda Leske,1 Ulrike Heinicke,1 Tilo Knape,2 Aimo Kannt,2,3 Verena Trümper,4 Kai Sohn,5 Annett Wilken-Schmitz,1 Holger Neb,1 Elisabeth H Adam,1 Volker Laux,2 Michael J Parnham,2 Valerie Onasch,4 Andreas Weigert,4 Kai Zacharowski,1,2 Andreas von Knethen1 1Goethe University Frankfurt, Department of Anaesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Frankfurt, Frankfurt, 60590, Germany; 2Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, 60596, Germany; 3Institute of Clinical Pharmacology, Goethe University, Frankfurt, 60590, Germany; 4Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, 60590, Germany; 5Innovation Field in-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, 70569, GermanyCorrespondence: Andreas von Knethen, Email andreas.vonknethen@ukffm.deBackground: COVID-19 is a serious viral infection, which is often associated with a lethal outcome. Therefore, understanding mechanisms, which affect the immune response during SARS-CoV2 infection, are important.Methods: To address this, we determined the number of T cells in peripheral blood derived from intensive care COVID-19 patients. Based on our previous studies, evaluating PPARγ-dependent T cell apoptosis in sepsis patients, we monitored PPARγ expression. We performed a next generation sequencing approach to identify putative PPARγ-target genes in Jurkat T cells and used a PPARγ transactivation assay in HEK293T cells. Finally, we translated these data to primary T cells derived from healthy donors.Results: A significantly reduced count of total CD3+ T lymphocytes and the CD4+ and CD8+ subpopulations was observed. Also, the numbers of anti-inflammatory, resolutive Th 2 cells and FoxP3-positive regulatory T cells (Treg) were decreased. We observed an augmented PPARγ expression in CD4+ T cells of intensive care COVID-19 patients. Adapted from a next generation sequencing approach in Jurkat T cells, we found the chemoattractant receptor‐homologous molecule expressed on T helper type 2 cells (CRTH2) as one gene regulated by PPARγ in T cells. This Th 2 marker is a receptor for prostaglandin D and its metabolic degradation product 15-deoxy-∆12,14-prostaglandin J2 (15d-PGJ2), an established endogenous PPARγ agonist. In line, we observed an increased PPARγ transactivation in response to 15d-PGJ2 treatment in HEK293T cells overexpressing CRTH2. Translating these data to primary T cells, we found that Th 2 differentiation was associated with an increased expression of CRTH2. Interestingly, these CRTH2+ T cells were prone to apoptosis.Conclusion: These mechanistic data suggest an involvement of PPARγ in Th 2 differentiation and T cell depletion in COVID-19 patients.Keywords: Treg, PPARγ, Th 2, COVID-19, NGS, IL-4, CRTH2, FoxP3 |
| format | Article |
| id | doaj-art-deb4c474a3804763b80e9aa908eb6669 |
| institution | OA Journals |
| issn | 2253-1556 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | ImmunoTargets and Therapy |
| spelling | doaj-art-deb4c474a3804763b80e9aa908eb66692025-08-20T02:18:27ZengDove Medical PressImmunoTargets and Therapy2253-15562024-11-01Volume 1359561696905Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 InfectionBecker ARöhrich KLeske AHeinicke UKnape TKannt ATrümper VSohn KWilken-Schmitz ANeb HAdam EHLaux VParnham MJOnasch VWeigert AZacharowski Kvon Knethen AAntonia Becker,1 Karoline Röhrich,1 Amanda Leske,1 Ulrike Heinicke,1 Tilo Knape,2 Aimo Kannt,2,3 Verena Trümper,4 Kai Sohn,5 Annett Wilken-Schmitz,1 Holger Neb,1 Elisabeth H Adam,1 Volker Laux,2 Michael J Parnham,2 Valerie Onasch,4 Andreas Weigert,4 Kai Zacharowski,1,2 Andreas von Knethen1 1Goethe University Frankfurt, Department of Anaesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Frankfurt, Frankfurt, 60590, Germany; 2Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt, 60596, Germany; 3Institute of Clinical Pharmacology, Goethe University, Frankfurt, 60590, Germany; 4Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, 60590, Germany; 5Innovation Field in-vitro Diagnostics, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Stuttgart, 70569, GermanyCorrespondence: Andreas von Knethen, Email andreas.vonknethen@ukffm.deBackground: COVID-19 is a serious viral infection, which is often associated with a lethal outcome. Therefore, understanding mechanisms, which affect the immune response during SARS-CoV2 infection, are important.Methods: To address this, we determined the number of T cells in peripheral blood derived from intensive care COVID-19 patients. Based on our previous studies, evaluating PPARγ-dependent T cell apoptosis in sepsis patients, we monitored PPARγ expression. We performed a next generation sequencing approach to identify putative PPARγ-target genes in Jurkat T cells and used a PPARγ transactivation assay in HEK293T cells. Finally, we translated these data to primary T cells derived from healthy donors.Results: A significantly reduced count of total CD3+ T lymphocytes and the CD4+ and CD8+ subpopulations was observed. Also, the numbers of anti-inflammatory, resolutive Th 2 cells and FoxP3-positive regulatory T cells (Treg) were decreased. We observed an augmented PPARγ expression in CD4+ T cells of intensive care COVID-19 patients. Adapted from a next generation sequencing approach in Jurkat T cells, we found the chemoattractant receptor‐homologous molecule expressed on T helper type 2 cells (CRTH2) as one gene regulated by PPARγ in T cells. This Th 2 marker is a receptor for prostaglandin D and its metabolic degradation product 15-deoxy-∆12,14-prostaglandin J2 (15d-PGJ2), an established endogenous PPARγ agonist. In line, we observed an increased PPARγ transactivation in response to 15d-PGJ2 treatment in HEK293T cells overexpressing CRTH2. Translating these data to primary T cells, we found that Th 2 differentiation was associated with an increased expression of CRTH2. Interestingly, these CRTH2+ T cells were prone to apoptosis.Conclusion: These mechanistic data suggest an involvement of PPARγ in Th 2 differentiation and T cell depletion in COVID-19 patients.Keywords: Treg, PPARγ, Th 2, COVID-19, NGS, IL-4, CRTH2, FoxP3https://www.dovepress.com/identification-of-crth2-as-a-new-ppar-target-gene-in-t-cells-suggested-peer-reviewed-fulltext-article-ITTtregpparγth2covid-19ngsil-4crth2foxp3 |
| spellingShingle | Becker A Röhrich K Leske A Heinicke U Knape T Kannt A Trümper V Sohn K Wilken-Schmitz A Neb H Adam EH Laux V Parnham MJ Onasch V Weigert A Zacharowski K von Knethen A Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 Infection ImmunoTargets and Therapy treg pparγ th2 covid-19 ngs il-4 crth2 foxp3 |
| title | Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 Infection |
| title_full | Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 Infection |
| title_fullStr | Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 Infection |
| title_full_unstemmed | Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 Infection |
| title_short | Identification of CRTH2 as a New PPARγ-Target Gene in T Cells Suggested CRTH2 Dependent Conversion of Th2 Cells as Therapeutic Concept in COVID-19 Infection |
| title_sort | identification of crth2 as a new ppar gamma target gene in t cells suggested crth2 dependent conversion of th2 cells as therapeutic concept in covid 19 infection |
| topic | treg pparγ th2 covid-19 ngs il-4 crth2 foxp3 |
| url | https://www.dovepress.com/identification-of-crth2-as-a-new-ppar-target-gene-in-t-cells-suggested-peer-reviewed-fulltext-article-ITT |
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