Early-Life Immune Programming Shapes Allergic Susceptibility

 

Yasutaka Motomura

Associated Professor,

Research Institute for Biomedical and Sciences, Tokyo University of Science

 

Immunoglobulin E (IgE) is thought to have evolved as a host defense mechanism against parasitic infections, mediating rapid immune responses and parasite expulsion via activation of mast cells and basophils. While beneficial under strict regulatory control, IgE responses can become pathogenic when this balance is disrupted by environmental changes, including dietary factors, leading to allergic disease. Thus, IgE lies at a critical immunological junction between parasite defense and allergy, and understanding its dysregulation is essential to elucidate allergic disease pathogenesis.

Epidemiological studies indicate that early-life events such as infantile dermatitis, antibiotic exposure, and dietary factors are associated with sustained IgE elevation and an increased lifetime risk of allergic disease. These findings suggest that environmental influences during infancy disrupt IgE regulation and promote long-term allergic predisposition. To investigate this, we established a mouse model of environmentally induced IgE production. Consistent with human observations, infantile dermatitis induced long-lasting IgE enhancement, which exacerbated allergic pathology in adulthood, demonstrating that early-life dysregulation of IgE control increases lifelong allergic susceptibility. Moreover, we identified a contribution of innate immune mechanisms to early-life IgE induction, revealing a previously unrecognized innate immune–driven IgE pathway. Elucidation of this mechanism may enable precise control of IgE responses for both allergy prevention and parasite defense.

 

Reference

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Hikichi, Y., Motomura, Y*., Takeuchi, O., Moro, K*. Posttranscriptional regulation of ILC2 homeostatic function via tristetraprolin. J Exp Med 218, (2021) *Co-coresponding