Trained immunity genes

This 2021 human cell study investigated trained immunity responses:

“We integrated genetic, epigenetic, and functional validation data to shed light on regulation of trained immunity responses. This data integration revealed a novel role of SIGLECs and KDM4 genes on trained immunity responses.

Siglec-5 is an inhibitory receptor that dampens the immune response, and was found to display reduced levels of activation mark H3K4me3 upon β-glucan training.

Siglec-14 has a ligand-binding domain almost identical to Siglec-5 but in contrast to Siglec-5, leads to activation of the inflammatory response. Differential expression of Siglec-14 has been shown to play a role in incidence of premature delivery in Group B Streptococcus-positive mothers, COPD exacerbation, and susceptibility to tuberculosis.

Within the family of histone demethylases, members of the KDM4 family showed the strongest association with trained immunity responses via modulation of methylation at H3K9.

We observed a high degree of inter-individual variability in both β-glucan and BCG-induced trained immunity responses in both cohorts. Age showed no correlation with induction of trained immunity, whereas male individuals showed higher trained immunity responses as assessed by measuring TNF-α production and IL-6.

By studying processes underlying heterogeneity of trained immunity responses, we prioritized and identified important candidate genes and pathways implicated in trained immunity that could be novel targets for diagnostic and therapeutic purposes. KDM4 demethylases and Siglecs are also considered attractive therapeutic targets in oncology and other immune cell-mediated diseases.”