Long-Term Programming of CD8 T Cell Immunity by Perinatal Exposure to Glucocorticoids

Jun Young Hong, Jaechul Lim, Fernando Carvalho, Jen Young Cho, Bharat Vaidyanathan, Shuang Yu, Charles Annicelli, W. K.Eddie Ip, Ruslan Medzhitov

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)847-861.e15
JournalCell
Volume180
Issue number5
DOIs
Publication statusPublished - 2020 Mar 5

Bibliographical note

Funding Information:
We thank Dr. Marcus Bosenberg for providing YUMMER1.7 cell line. We want to thank all current and former members of the Medzhitov lab for discussions. Work in the R.M. lab was supported by Howard Hughes Medical Institute (HHMI), the Blavatnik Family Foundation, the Else Kroner-Fresenius Foundation, and a grant from the NIH (1R01 AI144152-01). J.Y.H. is supported by the Cancer Research Institute/Bristol-Myers Squibb postdoctoral fellowship. J.L. is supported by Jane Coffin Childs Memorial Fund for Medical Research and the Human Frontier Science Program Long-Term Fellowship (LT000037/2018-L). J.Y.H. and R.M. designed the study, analyzed the data, and wrote the manuscript with input from the other co-authors. J.Y.H. performed experiments with the assistance from J.L. F.C. J.Y.C. B.V. S.Y. C.A. and W.K.E.I. J.L. performed all analyses of RNA-seq and ATAC-seq. F.C. performed all analyses of the brain histology. All authors declare no competing interests. B.V. is currently an employee of EMD Serono.

Funding Information:
We thank Dr. Marcus Bosenberg for providing YUMMER1.7 cell line. We want to thank all current and former members of the Medzhitov lab for discussions. Work in the R.M. lab was supported by Howard Hughes Medical Institute (HHMI), the Blavatnik Family Foundation , the Else Kroner-Fresenius Foundation , and a grant from the NIH ( 1R01 AI144152-01 ). J.Y.H. is supported by the Cancer Research Institute/Bristol-Myers Squibb postdoctoral fellowship. J.L. is supported by Jane Coffin Childs Memorial Fund for Medical Research and the Human Frontier Science Program Long-Term Fellowship ( LT000037/2018-L ).

Publisher Copyright:
© 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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