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  - 
TY  - JOUR
A1  - Boeckel, Hannah
A1  - Karsten, Christian M.
A1  - Göpel, Wolfgang
A1  - Herting, Egbert
A1  - Rupp, Jan
A1  - Härtel, Christoph
A1  - Hartz, Annika
T1  - Increased expression of anaphylatoxin C5a-receptor-1 in neutrophils and natural killer cells of preterm infants
JF  - International Journal of Molecular Sciences
N2  - Preterm infants are susceptible to infection and their defense against pathogens relies largely on innate immunity. The role of the complement system for the immunological vulnerability of preterm infants is less understood. Anaphylatoxin C5a and its receptors C5aR1 and -2 are known to be involved in sepsis pathogenesis, with C5aR1 mainly exerting pro-inflammatory effects. Our explorative study aimed to determine age-dependent changes in the expression of C5aR1 and C5aR2 in neonatal immune cell subsets. Via flow cytometry, we analyzed the expression pattern of C5a receptors on immune cells isolated from peripheral blood of preterm infants (n = 32) compared to those of their mothers (n = 25). Term infants and healthy adults served as controls. Preterm infants had a higher intracellular expression of C5aR1 on neutrophils than control individuals. We also found a higher expression of C5aR1 on NK cells, particularly on the cytotoxic CD56\(^{dim}\) subset and the CD56\(^-\) subset. Immune phenotyping of other leukocyte subpopulations revealed no gestational-age-related differences for the expression of and C5aR2. Elevated expression of C5aR1 on neutrophils and NK cells in preterm infants may contribute to the phenomenon of “immunoparalysis” caused by complement activation or to sustained hyper-inflammatory states. Further functional analyses are needed to elucidate the underlying mechanisms.
KW  - preterm infants
KW  - C5a
KW  - C5aR1
KW  - neutrophils
KW  - NK cells
KW  - innate immunity
KW  - sepsis
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-321196
SN  - 1422-0067
VL  - 24
IS  - 12
ER  -