TY  - JOUR
A1  - Pagel, Julia
A1  - Twisselmann, Nele
A1  - Rausch, Tanja K.
A1  - Waschina, Silvio
A1  - Hartz, Annika
A1  - Steinbeis, Magdalena
A1  - Olbertz, Jonathan
A1  - Nagel, Kathrin
A1  - Steinmetz, Alena
A1  - Faust, Kirstin
A1  - Demmert, Martin
A1  - Göpel, Wolfgang
A1  - Herting, Egbert
A1  - Rupp, Jan
A1  - Härtel, Christoph
T1  - Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants
JF  - Frontiers in Immunology
N2  - 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.
KW  - regulatory T cells
KW  - Tregs
KW  - bronchopulmonary dysplasia
KW  - BPD
KW  - preterm infant
KW  - neonate
KW  - Foxp3
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212409
SN  - 1664-3224
VL  - 11
ER  -