@article{PagelTwisselmannRauschetal.2020,
  author    = {Pagel, Julia and Twisselmann, Nele and Rausch, Tanja K. and Waschina, Silvio and Hartz, Annika and Steinbeis, Magdalena and Olbertz, Jonathan and Nagel, Kathrin and Steinmetz, Alena and Faust, Kirstin and Demmert, Martin and G{\"o}pel, Wolfgang and Herting, Egbert and Rupp, Jan and H{\"a}rtel, Christoph},
  title     = {Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.565257},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212409},
  year      = {2020},
  abstract  = {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 na{\"i}ve 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.},
  language  = {en}
}
@article{AlmanzarKleinSchmalzingetal.2016,
  author    = {Almanzar, Giovanni and Klein, Matthias and Schmalzing, Marc and Hilligardt, Deborah and El Hajj, Nady and Kneitz, Hermann and Wild, Vanessa and Rosenwald, Andreas and Benoit, Sandrine and Hamm, Henning and Tony, Hans-Peter and Haaf, Thomas and Goebeler, Matthias and Prelog, Martina},
  title     = {Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis},
  series = {International Archives of Allergy and Immunology},
  volume    = {171},
  journal   = {International Archives of Allergy and Immunology},
  number    = {2},
  issn      = {1018-2438},
  doi       = {10.1159/000450949},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196577},
  pages     = {141-154},
  year      = {2016},
  abstract  = {Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.},
  language  = {en}
}