2. Academic Validation
  3. CD11c+CD69+ trained APCs in lungs mediate allergic asthma through increased H3K27ac

CD11c+CD69+ trained APCs in lungs mediate allergic asthma through increased H3K27ac

  • Int Immunopharmacol. 2026 Jan 15:169:116021. doi: 10.1016/j.intimp.2025.116021.
Wenjian Li 1,  Junhai Wang 2,  Hanglin Li 2,  Boyang Zheng 3,  Beibei Qin 4,  Xiaoying Wang 5,  Ling Zhang 6,  Jiaqi Liang 2,  Jiao Li 7,  Yueling Wang 2,  Yuqing Deng 1,  Xiaoqing Zheng 1,  Ruihong Zeng 8
Affiliations

Affiliations

  • 1 Department of Immunology, Hebei Medical University, Zhongshan east road 361, Shijiazhuang 050017, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei, China.
  • 2 Department of Immunology, Hebei Medical University, Zhongshan east road 361, Shijiazhuang 050017, Hebei, China.
  • 3 Department of Immunology, Hebei Medical University, Zhongshan east road 361, Shijiazhuang 050017, Hebei, China; Department of Pharmacology, Hebei Medical University, Hebei, China.
  • 4 Department of Immunology, Hebei Medical University, Zhongshan east road 361, Shijiazhuang 050017, Hebei, China; Clinical Lab, Hebei Provincial People's Hospital, Hebei, China.
  • 5 Department of Pharmacology, Hebei Medical University, Hebei, China.
  • 6 Department of Immunology, Hebei Medical University, Zhongshan east road 361, Shijiazhuang 050017, Hebei, China; Medical laboratory center, Hebei Province Hospital of Traditional Chinese Medicine, Hebei, China.
  • 7 Department of Immunology, Hebei Medical University, Zhongshan east road 361, Shijiazhuang 050017, Hebei, China; Clinical Lab, the Second Affiliated Hospital of Hebei Medical University, Hebei, China.
  • 8 Department of Immunology, Hebei Medical University, Zhongshan east road 361, Shijiazhuang 050017, Hebei, China; Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Hebei, China. Electronic address: [email protected].
PMID: 41389664 DOI: 10.1016/j.intimp.2025.116021
Abstract

Objective: Investigating the impact and mechanism of trained antigen-presenting cells (APCs) in asthma in ovalbumin (OVA)-sensitized mouse model and discovering targets for treating asthma.

Methods: BALB/c and C57BL/6 J wild-type mice and TNF-α-/- mice were exposed to OVA. CD11c+CD69+ APCs induced by OVA were re-stimulated by lipopolysaccharide to investigate trained immunity. The effect of histone acetylation in CD11c+CD69+ trained APCs were determined in vivo and in vitro. Epigenetic inhibitors, TNF-α-/- mice, and adoptive transfer were used to explore the development and function of these cells in mice.

Results: OVA induced CD11c+CD69+ trained APCs, which showed stronger responses and lipid metabolic reprogramming characterized by increased acetylcarnitine, a source of acetyl, compared with CD11c+CD69- APCs in mice. CD11c+CD69+ trained APCs showed the histone acetylation marker H3K27achigh. H3K27ac was enriched at the CD69 gene in CD11c+CD69+ trained APCs, which supported CD69 expression. Histone Acetyltransferase Inhibitor inhibited development of CD11c+CD69+ trained APCs. Functionally, CD11c+CD69+ trained APCs promoted Th2-type response. Adoptively transferred CD11c+CD69+ trained APCs, but not CD11c+CD69- APCs, induced asthma. Inhibition of Histone Acetyltransferase prevented asthma. Further, TNF-α expression increased in asthmatic mice or patients. H3K27ac maintained TNF-α production in the trained APCs. TNF-α-/- mice showed attenuated asthma, whereas adoptive transfer of the trained APCs restored asthma, suggesting a key role of TNF-α for the function of the trained APCs.

Conclusion: We discovered a crucial role of CD11c+CD69+ trained APCs in asthma, and demonstrated that histone acetylation supported CD11c+CD69+ trained APCs to mediate asthma. The result may provide a potential target for the treatment of asthma.

Keywords

Allergic asthma; H3K27ac; Metabolic reprogramming; TNF-α; Trained APCs.

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