Developmental origins of inflammatory and immune diseases

Abstract

Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the 'developmental programming' and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfunction may in turn lead offspring to be susceptible to inflammatory and immune diseases in adulthood. These facts suggest that inflammatory and immune disorders might have developmental origins. In recent years, inflammatory and immune disorders have become a growing health problem worldwide. However, there is no systematic report in the literature on the developmental origins of inflammatory and immune diseases and the potential mechanisms involved. Here, we review the impacts of adverse intrauterine environments on the immune function in offspring. This review shows the results from human and different animal species and highlights the underlying mechanisms, including damaged development of cells in the thymus, helper T cell 1/helper T cell 2 balance disturbance, abnormal epigenetic modification, effects of maternal glucocorticoid overexposure on fetal lymphocytes and effects of the fetal hypothalamic-pituitary-adrenal axis on the immune system. Although the phenomena have already been clearly implicated in epidemiologic and experimental studies, new studies investigating the mechanisms of these effects may provide new avenues for exploiting these pathways for disease prevention.

Keywords: T cells; adverse intrauterine environment; developmental origins; inflammatory and immune diseases; thymus.

Figure 1

Developmental origins of inflammatory and immune disorders. Prenatal stress, psychosocial stress and xenobiotics exposure may affect the development of the fetal immune system, through affecting immune cells, epigenetic modification of immune-related genes or other physiological systems that regulate immune responses. As a result, immune dysfunction may increase susceptibility to inflammatory and immune diseases in offspring and even into adulthood. GC: glucocorticoid; HPA: hypothalamic–pituitary–adrenal; TH1/2: helper T 1/helper T 2.