Investigating the Epigenetic Regulation of Innate Immune Memory

Authors

Emily Nguyen, University of HoustonFollow
Heather L. Caslin, University of HoustonFollow

Abstract

Innate immune memory is the ability of innate immune cells, such as monocytes and macrophages, to develop “memory” that allows them to respond more efficiently when (re-)exposed to a second stimulus. Innate immune memory is driven by epigenetic changes, including histone methylation (H3K4me3) and acetylation (H3K27ac), which can activate gene transcription at inflammatory loci and drive enhanced activation to a second stimulus. While we have previously shown that macrophage cell cultures treated with palmitate exhibit increased cytokine production and metabolism (outcomes of innate immune), the specific epigenetic mechanisms regulating these changes have not been shown. PURPOSE: This study aimed to determine if H3K27ac and H3K4me3 increase following palmitate-induced innate immune memory. METHODS: Bone marrow was collected from mouse femurs and used to culture bone marrow-derived macrophages for 5–8 days at 37°C. Cells were treated with palmitate or DMSO (control) for 24 hours, followed by a 5-day washout period to induce innate immune memory. Half of the cells were used for histone analysis via flow cytometry. The remaining cells were used to confirm the induction of a memory phenotype. The cells were activated with 50 ng/mL LPS for 24 hours and the media was collected for cytokine analysis using ELISA. RESULTS: ELISA analysis showed that prior palmitate treatment increased LPS-induced TNF-α production compared to cells treated with DMSO (pCONCLUSION: This study demonstrates that palmitate-induced innate immune memory may occur through elevated H3K27ac and/or H3K4me3. Moreover, our findings suggest that innate immune memory can be measured by flow cytometry using antibodies to these specific modifications in our culture model. Future work will investigate the induction of these histone modifications in innate immune memory to weight loss. Additionally, we will determine whether interventions such as exercise or metformin can alter these modifications and potentially reverse innate immune memory, paving the way for targeted approaches to modulate immune responses.

Recommended Citation

Nguyen, Emily and Caslin, Heather L. (2025) "Investigating the Epigenetic Regulation of Innate Immune Memory," International Journal of Exercise Science: Conference Proceedings: Vol. 2: Iss. 17, Article 82.
Available at: https://digitalcommons.wku.edu/ijesab/vol2/iss17/82