Long-term programming of CD8 T cell immunity by perinatal exposure to glucocorticoids

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.

Cell 180: 847-861.e15 (2020).

Age-dependent type 2 immune response to the rhinovirus leads to asthma development in neonates

Early-life respiratory infection has been associated with asthma in later-life. Particularly, early-life human rhinovirus (RV) infection has been linked to asthma development in high risk infants and children. Nevertheless, the role of RV infection in the initiation of asthma remains unclear. In Dr. Hong's doctoral research, RV infection in neonatal mice induces type 2 immune response, while infection in adult mice elicits type 1 immune response. Age-dependent induction of type 2 cytokines, such as IL-25, IL-33, and IL-33 leads to the increase of type 2 innate lymphoid cells (ILC2). Type 1 cytokine, IFN-γ, is able to reduce the function of ILC2 in type 2 immune response. Finally, neonatal RV infection provokes persistent mucous metaplasia and airway hyperresponsiveness, the asthma-phenotype, which is not observed in adulthood infection. These results suggest that early-life RV infection can contribute to the initiation of persistent asthma by provoking age-dependent type 2 immune response.