Defining Early Life Stress as a Precursor for Autoimmune Disease

Abstract

Childhood exposure to traumatic events, termed early life stress (ELS), is now widely recognized for causing long-term negative health effects that may not manifest until adulthood. Allostatic load (AL) describes the cumulative "wear-and-tear" effects of chronic stress on the body that may adversely affect human health by accelerating other disease processes. Recent epidemiological studies have reported higher stress levels in industrialized countries and trends of increasing prevalence in autoimmune diseases during recent decades. To elucidate mechanisms of stress-related immune dysregulation, most animal studies up to now have focused on AL and stress-triggered events occurring in adults but have not explored ELS in the context of autoimmune disorders. We have identified a current gap in understanding the impact of ELS on immune system ontogeny and its potential for priming genetically susceptible individuals who are at increased risk for autoimmune diseases later in life, through mechanisms involving neuroendocrine-immune cross talk. In this review, we highlight the intersection between stress and immune function, with a focus on ELS as consequential for increased autoimmune disorder risks later in life.

FIG. 1:

Number of citations during 1949 to 2019 for searched terms “psychological stress” and “autoimmune disease”

FIG. 2:

Hypothetical model of stress and thymic development with AD risks. Depicts the increased risk of AD resulting from stress-induced dysfunction of thymic T-cell development, resulting in polarization of proinflammatory Th17 self-reactive mediators amid a shortage of Treg cell lineage of CD4⁺ T lymphocytes as a determinant of AD. CD, cluster of differentiation; CNS, central nervous system; DN, double negative; DP, double positive; Th, T helper; Treg, regulatory T.