Sleep and diet emerge as key drivers of immunome variation

Immunome (immune cells and functions) variations are closely related to human health. Various exposures, including the external environment and personal lifestyles, are important factors affecting the immune system.

Recent advances in research have focused on immune system variation mainly from a genome perspective. This population-based study (N=1,001 from The Human Phenome Atlas (THPA) cohort) investigated the immune variability from an exposure perspective, and further focused on the roles of the transcriptome and metabolome.

The study found that exposures explain 10.74% of the immunome variation. Through systematic association analyses, they identified 55 immunophenotypes that were influenced by 20 single or 3 composite exposures, with sleep and diet emerging as dominant exposures affecting the immunome. Sleep and diet influence the proportions of innate immune cells and the expression levels of immune cell surface proteins such as CD85j and CD16, respectively. Notably, distinct from the increase in IL-1β secretion caused by short-term late sleep onset, long-term late sleep onset triggered chronic inflammation with more metabolic changes. Bi-directional mediation analysis revealed that the effects of sleep on immunity are commonly linked to the transcriptome, whereas dietary influences on immunity are primarily associated with the metabolome. By summing weighted scores of molecules in mediation linkages, they developed transcriptomic (T-) and metabolomic (M-) indexes and further demonstrated that these indexes reflect human immune health or chronic diseases.

In summary, this study systemically charted a map of exposure-immunophenotype associations, highlighting transcriptional and metabolic molecules that interact with immunophenotypes under exposure influences. These findings are expected to provide guidance for future health assessment and management.