TY - JOUR
T1 - Long-Term Programming of CD8 T Cell Immunity by Perinatal Exposure to Glucocorticoids
AU - Hong, Jun Young
AU - Lim, Jaechul
AU - Carvalho, Fernando
AU - Cho, Jen Young
AU - Vaidyanathan, Bharat
AU - Yu, Shuang
AU - Annicelli, Charles
AU - Ip, W. K.Eddie
AU - Medzhitov, Ruslan
N1 - Publisher Copyright:
© 2020
PY - 2020/3/5
Y1 - 2020/3/5
N2 - Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity. Early life glucocorticoid exposure has long-term effects on immunity, including diminished CD8+ T cell responses in adulthood and impaired control of tumor growth as well as infection.
AB - Early life environmental exposure, particularly during perinatal period, can have a life-long impact on organismal development and physiology. The biological rationale for this phenomenon is to promote physiological adaptations to the anticipated environment based on early life experience. However, perinatal exposure to adverse environments can also be associated with adult-onset disorders. Multiple environmental stressors induce glucocorticoids, which prompted us to investigate their role in developmental programming. Here, we report that perinatal glucocorticoid exposure had long-term consequences and resulted in diminished CD8 T cell response in adulthood and impaired control of tumor growth and bacterial infection. We found that perinatal glucocorticoid exposure resulted in persistent alteration of the hypothalamic-pituitary-adrenal (HPA) axis. Consequently, the level of the hormone in adults was significantly reduced, resulting in decreased CD8 T cell function. Our study thus demonstrates that perinatal stress can have long-term consequences on CD8 T cell immunity by altering HPA axis activity. Early life glucocorticoid exposure has long-term effects on immunity, including diminished CD8+ T cell responses in adulthood and impaired control of tumor growth as well as infection.
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U2 - 10.1016/j.cell.2020.02.018
DO - 10.1016/j.cell.2020.02.018
M3 - Article
C2 - 32142678
AN - SCOPUS:85080151931
SN - 0092-8674
VL - 180
SP - 847-861.e15
JO - Cell
JF - Cell
IS - 5
ER -