Evidence map›Paper›PMID 41735318›Full record

ArticleNature communications2026

DNA-PK-mediated phosphorylation of STAT6 establishes a non-canonical type 2 immunity axis to prevent macrophage senescence.

Zhao Zhou, Xinmeng Li, Yushuang Wang, Long Liang, Chunyang Wang, Yongchang Sun, Dongmei Wu, Yifu Qiu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Zhao ZhouState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
Xinmeng LiState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
Yushuang WangState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
Long LiangDepartment of Respiratory and Critical Care Medicine, Peking University Third Hospital and Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China.
Chunyang WangState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
Yongchang SunDepartment of Respiratory and Critical Care Medicine, Peking University Third Hospital and Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, China. suny@bjmu.edu.cn.
Dongmei WuState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China. dongmei.wu@pku.edu.cn.ORCID http://orcid.org/0009-0008-3370-3729
Yifu QiuState Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China. yifu.qiu@pku.edu.cn.ORCID http://orcid.org/0000-0001-5645-3189

Funding

Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2018YFA0800702Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2021YFA0804801Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2024YFA1802103
6 · The paper itself

Abstract

Macrophage senescence drives inflammaging, a chronic, age-related inflammation. To date, the protective mechanisms against inflammaging are poorly defined. Here, we identify DNA-PK-mediated phosphorylation of murine STAT6 at serine 807 (Ser807) as a crucial post-translational modification for preventing macrophage senescence. Ser807 phosphorylation blocks STAT6 ubiquitination-mediated degradation and promotes STAT6 partnering with PU.1 to activate DNA repair genes. Macrophages lacking Ser807 phosphorylation exhibit DNA repair defects, undergo senescence, and fuel inflammaging. In vivo, the phosphor-null STAT6 mutant (STAT6(S807A)) accelerates macrophage senescence, tissue fibrosis, and systemic aging. Adoptive transfer of phosphomimetic STAT6(S807E)-expressing macrophages rescues accelerated aging. Importantly, phosphorylation of human STAT6 at the homologous residue (Ser817) is significantly reduced in the lungs of patients with chronic obstructive pulmonary disease (COPD), correlating with increased DNA damage and senescence. Thus, our findings reveal a DNA-PK-STAT6 axis enacting a non-canonical type 2 immunity via DNA repair to prevent macrophage senescence, presenting a therapeutic target for healthy aging.

Indexed as

Cellular SenescenceDNA-Activated Protein KinaseMacrophagesSTAT6 Transcription FactorAgingAnimalsDNA-Binding ProteinsDNA DamageDNA RepairHumansMaleMiceMice, Inbred C57BLPhosphorylationProto-Oncogene ProteinsProto-Oncogene Protein Spi-1DNA-Activated Protein KinaseDNA-Binding ProteinsPrkdc protein, mouseProto-Oncogene ProteinsProto-Oncogene Protein Spi-1STAT6 protein, humanStat6 protein, mouseSTAT6 Transcription FactorTrans-Activators

Identifiers

PMID41735318
PMCPMC13044253

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.