Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants
Regulatory T cells (Tregs) are important for the ontogenetic control of immune activation and tissue damage in preterm infants. However, the role of Tregs for the development of bronchopulmonary dysplasia (BPD) is yet unclear. The aim of our study was to characterize CD4+ CD25+ forkhead box protein...
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.565257/full |
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| author | Julia Pagel Julia Pagel Julia Pagel Julia Pagel Nele Twisselmann Tanja K. Rausch Tanja K. Rausch Silvio Waschina Annika Hartz Magdalena Steinbeis Jonathan Olbertz Kathrin Nagel Alena Steinmetz Kirstin Faust Martin Demmert Wolfgang Göpel Egbert Herting Jan Rupp Jan Rupp Christoph Härtel Christoph Härtel Christoph Härtel Christoph Härtel |
| author_facet | Julia Pagel Julia Pagel Julia Pagel Julia Pagel Nele Twisselmann Tanja K. Rausch Tanja K. Rausch Silvio Waschina Annika Hartz Magdalena Steinbeis Jonathan Olbertz Kathrin Nagel Alena Steinmetz Kirstin Faust Martin Demmert Wolfgang Göpel Egbert Herting Jan Rupp Jan Rupp Christoph Härtel Christoph Härtel Christoph Härtel Christoph Härtel |
| author_sort | Julia Pagel |
| collection | DOAJ |
| description | Regulatory T cells (Tregs) are important for the ontogenetic control of immune activation and tissue damage in preterm infants. However, the role of Tregs for the development of bronchopulmonary dysplasia (BPD) is yet unclear. The aim of our study was to characterize CD4+ CD25+ forkhead box protein 3 (FoxP3)+ Tregs in peripheral blood of well-phenotyped preterm infants (n = 382; 23 + 0 – 36 + 6 weeks of gestational age) with a focus on the first 28 days of life and the clinical endpoint BPD (supplemental oxygen for longer than 28 days of age). In a subgroup of preterm infants, we characterized the immunological phenotype of Tregs (n = 23). The suppressive function of Tregs on CD4+CD25- T cells was compared in preterm, term and adult blood. We observed that extreme prematurity was associated with increased Treg frequencies which peaked in the second week of life. Independent of gestational age, increased Treg frequencies were noted to precede the development of BPD. The phenotype of preterm infant Tregs largely differed from adult Tregs and displayed an overall naïve Treg population (CD45RA+/HLA-DR-/Helios+), especially in the first days of life. On day 7 of life, a more activated Treg phenotype pattern (CCR6+, HLA-DR+, and Ki-67+) was observed. Tregs of preterm neonates had a higher immunosuppressive capacity against CD4+CD25- T cells compared to the Treg compartment of term neonates and adults. In conclusion, our data suggest increased frequencies and functions of Tregs in preterm neonates which display a distinct phenotype with dynamic changes in the first weeks of life. Hence, the continued abundance of Tregs may contribute to sustained inflammation preceding the development of BPD. Functional analyses are needed in order to elucidate whether Tregs have potential as future target for diagnostics and therapeutics. |
| first_indexed | 2024-12-24T03:13:57Z |
| format | Article |
| id | doaj.art-612ba4e4506343a58d71cc32e101bee5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-24T03:13:57Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-612ba4e4506343a58d71cc32e101bee52022-12-21T17:17:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.565257565257Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm InfantsJulia Pagel0Julia Pagel1Julia Pagel2Julia Pagel3Nele Twisselmann4Tanja K. Rausch5Tanja K. Rausch6Silvio Waschina7Annika Hartz8Magdalena Steinbeis9Jonathan Olbertz10Kathrin Nagel11Alena Steinmetz12Kirstin Faust13Martin Demmert14Wolfgang Göpel15Egbert Herting16Jan Rupp17Jan Rupp18Christoph Härtel19Christoph Härtel20Christoph Härtel21Christoph Härtel22Department of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, GermanyGerman Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck, GermanyDepartment of Pediatrics, University Hospital Hamburg-Eppendorf, Hamburg, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Medical Biometry and Statistics, University of Lübeck, Lübeck, GermanyResearch Group Medical Systems Biology, Christian-Albrechts-University Kiel, Kiel, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyDepartment of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, GermanyGerman Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck, GermanyDepartment of Pediatrics, University of Lübeck, Lübeck, GermanyGerman Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Lübeck, GermanyUniversity Children's Hospital, University of Würzburg, Würzburg, GermanyPRIMAL (Priming Immunity at the Beginning of Life) Consortium, Lübeck, GermanyRegulatory T cells (Tregs) are important for the ontogenetic control of immune activation and tissue damage in preterm infants. However, the role of Tregs for the development of bronchopulmonary dysplasia (BPD) is yet unclear. The aim of our study was to characterize CD4+ CD25+ forkhead box protein 3 (FoxP3)+ Tregs in peripheral blood of well-phenotyped preterm infants (n = 382; 23 + 0 – 36 + 6 weeks of gestational age) with a focus on the first 28 days of life and the clinical endpoint BPD (supplemental oxygen for longer than 28 days of age). In a subgroup of preterm infants, we characterized the immunological phenotype of Tregs (n = 23). The suppressive function of Tregs on CD4+CD25- T cells was compared in preterm, term and adult blood. We observed that extreme prematurity was associated with increased Treg frequencies which peaked in the second week of life. Independent of gestational age, increased Treg frequencies were noted to precede the development of BPD. The phenotype of preterm infant Tregs largely differed from adult Tregs and displayed an overall naïve Treg population (CD45RA+/HLA-DR-/Helios+), especially in the first days of life. On day 7 of life, a more activated Treg phenotype pattern (CCR6+, HLA-DR+, and Ki-67+) was observed. Tregs of preterm neonates had a higher immunosuppressive capacity against CD4+CD25- T cells compared to the Treg compartment of term neonates and adults. In conclusion, our data suggest increased frequencies and functions of Tregs in preterm neonates which display a distinct phenotype with dynamic changes in the first weeks of life. Hence, the continued abundance of Tregs may contribute to sustained inflammation preceding the development of BPD. Functional analyses are needed in order to elucidate whether Tregs have potential as future target for diagnostics and therapeutics.https://www.frontiersin.org/article/10.3389/fimmu.2020.565257/fullregulatory T cellsTregsbronchopulmonary dysplasiaBPDpreterm infantneonate |
| spellingShingle | Julia Pagel Julia Pagel Julia Pagel Julia Pagel Nele Twisselmann Tanja K. Rausch Tanja K. Rausch Silvio Waschina Annika Hartz Magdalena Steinbeis Jonathan Olbertz Kathrin Nagel Alena Steinmetz Kirstin Faust Martin Demmert Wolfgang Göpel Egbert Herting Jan Rupp Jan Rupp Christoph Härtel Christoph Härtel Christoph Härtel Christoph Härtel Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants Frontiers in Immunology regulatory T cells Tregs bronchopulmonary dysplasia BPD preterm infant neonate |
| title | Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants |
| title_full | Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants |
| title_fullStr | Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants |
| title_full_unstemmed | Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants |
| title_short | Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants |
| title_sort | increased regulatory t cells precede the development of bronchopulmonary dysplasia in preterm infants |
| topic | regulatory T cells Tregs bronchopulmonary dysplasia BPD preterm infant neonate |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.565257/full |
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