The transcription factor NF-Y promotes myeloid cell survival and protects from inflammatory vascular disease.

Authors

Carlos Silvestre-Roig, José M González-Granado, Collins Osei-Sarpong, Eva Gricar, Pilar Gonzalo, Merieme Farjia, Mariano Malamud, Lina-Marie Vöcking, Noelia Alonso-Gonzalez, Raphael Chevre, Vanesa Esteban, Vicente Andrés

Published in

Journal of leukocyte biology. Aug 14, 2026. Epub Aug 14, 2026.

Abstract

Myeloid cells orchestrate vascular inflammation through transcriptional programs that control their maturation, effector function, and survival. While lineage-determining transcription factors establish myeloid identity, our understanding of the transcriptional regulation of myeloid cell behavior in chronic inflammatory contexts remains limited. Nuclear factor-Y (NF-Y) is a trimeric CCAAT-binding transcription factor that regulates cell proliferation and differentiation and is essential for maintaining stem and progenitor cell fitness. Here, we investigate NF-Y activity in myeloid cell function and survival using integrated single-cell transcriptomics and myeloid-specific deletion of the NF-YA subunit. At RNA level, NF-Y subunit transcripts were detected across myeloid compartments, with NF-YA enriched in proliferative macrophages and immature neutrophils. In mouse atherosclerotic lesions, low NF-YA levels were associated with macrophages exhibiting lipid-handling and phagocytic signatures and with neutrophils displaying a proinflammatory phenotype. NF-Y deficiency impaired neutrophil adhesion and rolling, increased their susceptibility to apoptosis, and promoted activation and lipid accumulation in macrophages. In vivo, myeloid NF-YA deficiency reduced circulating neutrophil counts, increased macrophage and neutrophil apoptosis during acute inflammation, expanded necrotic cores, leading to larger and more unstable atherosclerotic lesions, and aggravated both atherosclerosis and injury-induced neointimal thickening. These findings identify NF-Y as a transcriptional safeguard of myeloid cell survival during inflammatory stress, thereby shaping disease progression and outcomes in vascular disease.

PMID:
42600095
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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