Effect of prenatal steroid treatment on the developing immune system
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Effect of prenatal steroid treatment on the developing immune system. / Diepenbruck, Ines; Much, Chressen C; Krumbholz, Aniko; Kolster, Manuela; Thieme, René; Thieme, Detlef; Diepenbruck, Silke; Solano, M Emilia; Arck, Petra C; Tolosa, Eva.
In: J MOL MED, Vol. 91, No. 11, 01.11.2013, p. 1293-302.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Effect of prenatal steroid treatment on the developing immune system
AU - Diepenbruck, Ines
AU - Much, Chressen C
AU - Krumbholz, Aniko
AU - Kolster, Manuela
AU - Thieme, René
AU - Thieme, Detlef
AU - Diepenbruck, Silke
AU - Solano, M Emilia
AU - Arck, Petra C
AU - Tolosa, Eva
PY - 2013/11/1
Y1 - 2013/11/1
N2 - UNLABELLED: Prenatal steroids have an undisputed positive effect of decreasing neonatal morbidity and mortality by improving fetal lung maturation. Some concerns have been raised on long-term consequences on the hypothalamic-pituitary-adrenal axis and cognition, but there are no studies addressing effects on the immune system. The thymus is an essential organ for the development and selection of T cells, and thymocytes are extremely sensitive to steroids. Using a mouse model for prenatal steroid administration, we show here that betamethasone treatment to the mother has a profound effect on the thymus of the offspring. We find the thymus volume reduced, affecting mostly the developing CD4+ CD8+ double-positive thymocytes and a compensatory accelerated transition of the earlier stages to replenish the depleted compartment. This effect lasts for at least 3 days, which correspond to a very relevant period for the selection of the T cell repertoire. Moreover, we show that low doses of betamethasone have similar effects on human thymocytes in vitro. Therefore, further studies are needed to analyze possible long-term consequences of this treatment on the immune system of the offspring.KEY MESSAGE: Betamethasone administered to the mother before birth reaches the fetal thymus. Prenatal betamethasone results in massive loss of developing thymocytes. The effects of betamethasone on thymus development are visible for several days. Human thymocytes are also sensitive to low doses of betamethasone. Altered thymocyte development around birth may have an effect on the immune system.
AB - UNLABELLED: Prenatal steroids have an undisputed positive effect of decreasing neonatal morbidity and mortality by improving fetal lung maturation. Some concerns have been raised on long-term consequences on the hypothalamic-pituitary-adrenal axis and cognition, but there are no studies addressing effects on the immune system. The thymus is an essential organ for the development and selection of T cells, and thymocytes are extremely sensitive to steroids. Using a mouse model for prenatal steroid administration, we show here that betamethasone treatment to the mother has a profound effect on the thymus of the offspring. We find the thymus volume reduced, affecting mostly the developing CD4+ CD8+ double-positive thymocytes and a compensatory accelerated transition of the earlier stages to replenish the depleted compartment. This effect lasts for at least 3 days, which correspond to a very relevant period for the selection of the T cell repertoire. Moreover, we show that low doses of betamethasone have similar effects on human thymocytes in vitro. Therefore, further studies are needed to analyze possible long-term consequences of this treatment on the immune system of the offspring.KEY MESSAGE: Betamethasone administered to the mother before birth reaches the fetal thymus. Prenatal betamethasone results in massive loss of developing thymocytes. The effects of betamethasone on thymus development are visible for several days. Human thymocytes are also sensitive to low doses of betamethasone. Altered thymocyte development around birth may have an effect on the immune system.
KW - Animals
KW - Animals, Newborn
KW - Betamethasone
KW - Female
KW - Fetus
KW - Glucocorticoids
KW - Humans
KW - Male
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Organ Size
KW - Pregnancy
KW - T-Lymphocytes
KW - Thymus Gland
U2 - 10.1007/s00109-013-1069-2
DO - 10.1007/s00109-013-1069-2
M3 - SCORING: Journal article
C2 - 23851605
VL - 91
SP - 1293
EP - 1302
JO - J MOL MED
JF - J MOL MED
SN - 0946-2716
IS - 11
ER -