Work

Interferon regulatory factor 1: a key transcriptional node orchestrating macrophage polarization: mechanisms and therapeutic potential

Year: 2026

Type: review

Abstract: Macrophageexhibit remarkable functional plasticity and adopt M1-like pro-inflammatory or M2-like anti-inflammatory/pro-resolving states in response to microenvironmental stimuli. Notably, this binary functional classification originates largely from in-vitro experimental systems; tissue-resident macrophages in vivo display a continuous spectrum of activation phenotypes rather than discrete subsets. Dysregulated macrophage polarization drives the pathogenesis of infectious diseases, malignancies, and metabolic-inflammatory disorders. Interferon regulatory factor 1 (IRF1) is a pivotal transcription factor governing macrophage fate, yet its multilayered regulatory circuits and context-dependent dual impacts on M1-like and M2-like transcriptional programs remain to be systematically summarized. This review synthesizes recent advances in IRF1-centered regulatory networks of macrophage polarization. We recapitulate IRF1 crosstalk with core signaling cascades including JAK/STAT, TLR/MyD88 and IFN-γ pathways, as well as its transcriptional control of target genes such as iNOS, IL-12, and CXCL10. Multi-layer regulatory mechanisms modulating IRF1 activity are outlined, including transcriptional, epigenetic, non-coding-RNA-mediated post-transcriptional, and post-translational modifications. We further dissect IRF1-linked immunometabolic reprogramming and epigenetic remodeling, and describe its versatile pathophysiological roles in infection, cancer and metabolic inflammatory diseases based on multi-omics and single-cell sequencing evidence. Collectively, this review illustrates IRF1 as a key transcriptional node that orchestrates macrophage polarization, and highlights prospective therapeutic targets and intervention strategies for IRF1-associated immune-mediated disorders.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1884705

Authors: Shuqi Cao, Shuang Feng, Yue Gao, Zhiyuan Sun, Shiyao Bai, Xinming Su

Institution: First Hospital of China Medical University

Language: English

Topic: Immune cells in cancer

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801