Abstract
The molecular machinery controlling immune development has been extensively investigated. Studies in animal models and adult individuals have revealed fundamental mechanisms of disease and have been essential to understanding how humans sense and respond to cellular stress, tissue damage, pathogens and their environment. Nonetheless, our understanding of how immune responses originate during human development is just starting to emerge. In particular, studies to unveil how environmental and other non-heritable factors shape the immune system at the beginning of life offer great promise to yield important knowledge about determinants of normal inter-individual immune variation and to prevent and treat many human diseases. In this review, we summarize our current understanding of some of the mechanisms determining early life antibody production as a model of an immune process with sequential molecular checkpoints susceptible to influence by non-heritable factors. We discuss the potential of epigenomics as a valuable approach that may reveal not only relevant gene-environment interactions but important clues about immune developmental processes and homeostasis in early life. We then highlight the novel paradigm of human immunology as a complex field that nowadays requires a longitudinal systems-biology approach to understand normal variation and developmental changes during the first few years of life.
Highlights
Mechanistic studies conducted over the past three decades have defined the basic molecular machinery that controls the development of protective immune responses in different cell populations [1,2,3]
We discuss the novel paradigm of human immunology as a complex field that nowadays requires a longitudinal systems-level biology focus, including the study of epigenetic variation and changes during the first few years of life
Antibody production is controlled by a stereotypical developmental program that includes cardinal molecules that drive cell-specific proliferation, survival, and differentiation (e.g., tumor necrosis factor superfamily of cytokines (TNFSF) and tumor necrosis factors (TNFs) receptor superfamily (TNFRSF)) and specific transcription factors. Changes in these critical checkpoints can potentially shape the development of the immune system and allow dynamic epigenetic fine-tuning occurring in response to the environmental influence during early life
Summary
Mechanistic studies conducted over the past three decades have defined the basic molecular machinery that controls the development of protective immune responses in different cell populations [1,2,3]. Changes in these critical checkpoints can potentially shape the development of the immune system and allow dynamic epigenetic fine-tuning occurring in response to the environmental influence during early life.
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