ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1621440
This article is part of the Research TopicGenetic Code of Defense: Unravelling Molecular Mechanism in Innate ImmunityView all articles
Deficiency of HMGN2 enhances antibacterial activity of macrophages by promoting H3 histone modification-mediated CD14/iNOS expression
Provisionally accepted
- 1Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- 2Sichuan Provincial People's Hospital, Chengdu, China
- 3Sichuan university, Chengdu, China
- 4North Sichuan Medical College, Nanchong, China
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High-mobility group nucleosomal-binding domain 2 (HMGN2) is a widely recognized chromatin-structural protein within the nucleus of eukaryotes. It has been demonstrated to be implicated in immune responses during bacterial infection. Nevertheless, the regulatory mechanism of HMGN2 in the antibacterial process of macrophages remains unclear. In this research, distinct alterations in HMGN2 expression in macrophages were observed subsequent to microbial stimulation. To investigate the role of HMGN2 in macrophages during infection, the CRISPR-Cas9 technology was employed to construct an HMGN2-knockout RAW264.7 cell line. It was verified that HMGN2 knockout could significantly enhance the bactericidal and phagocytic capabilities of macrophages. The mechanistic investigation revealed that cluster of differentiation 14 (CD14) was transcriptionally promoted in HMGN2-knockout macrophages. HMGN2 knockout regulates CD14 expression by augmenting histone epigenetic modification levels on the CD14 gene promoter, including H3K4me3, H3K9ac, and H3K27ac. Moreover, HMGN2 knockout can activate the CD14-mediated mitogen-activated protein kinase (MAPK) signaling pathways to facilitate nitric oxide (NO) production. This study uncovers a crucial role of HMGN2 in the macrophage-mediated host immune response. HMGN2 is anticipated to serve as a therapeutic target for the treatment of infectious diseases.
Keywords: HMGN2, macrophage, CD14, epigenetic modification, Nitric Oxide
Received: 01 May 2025; Accepted: 21 Oct 2025.
Copyright: © 2025 Yang, Zhang, Liu, Huang, Teng and Miao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Junming Miao, miaojunming@nsmc.edu.cn
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