Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, the Netherlands.
Akthelia Pharmaceuticals, Grandagardi 16, 101 Reykjavik, Iceland.
Drug Discov Today. 2024 Nov;29(11):104193. doi: 10.1016/j.drudis.2024.104193. Epub 2024 Sep 26.
Innate immunity plays an important role in host defense against pathogenic infections. It involves macrophage polarization into either the pro-inflammatory M1 or the anti-inflammatory M2 phenotype, influencing immune stimulation or suppression, respectively. Epigenetic changes during immune reactions contribute to long-term innate immunity imprinting on macrophage polarization. It is becoming increasingly evident that epigenetic modulators, such as histone deacetylase (HDAC) inhibitors (HDACi), enable the enhancement of innate immunity by tailoring macrophage polarization in response to immune stressors. In this review, we summarize current literature on the impact of HDACi and other epigenetic modulators on the functioning of macrophages during diseases that have a strong immune component, such as infections. Depending on the disease context and the chosen therapeutic intervention, HDAC1, HDAC2, HDAC3, HDAC6, or HDAC8 are particularly important in influencing macrophage polarization towards either M1 or M2 phenotypes. We anticipate that therapeutic strategies based on HDAC epigenetic mechanisms will provide a unique approach to boost immunity against disease challenges, including resistant infections.
先天免疫在宿主防御病原体感染中起着重要作用。它涉及巨噬细胞向促炎 M1 或抗炎 M2 表型的极化，分别影响免疫刺激或抑制。免疫反应过程中的表观遗传变化有助于长期的先天免疫在巨噬细胞极化上的印记。越来越明显的是，表观遗传调节剂，如组蛋白去乙酰化酶 (HDAC) 抑制剂 (HDACi)，通过调整巨噬细胞极化来应对免疫应激，从而增强先天免疫。在这篇综述中，我们总结了目前关于 HDACi 和其他表观遗传调节剂在具有强烈免疫成分的疾病（如感染）期间对巨噬细胞功能的影响的文献。根据疾病的背景和选择的治疗干预，HDAC1、HDAC2、HDAC3、HDAC6 或 HDAC8 在影响巨噬细胞向 M1 或 M2 表型极化方面尤为重要。我们预计，基于 HDAC 表观遗传机制的治疗策略将为增强免疫以应对疾病挑战（包括耐药感染）提供一种独特的方法。
