Acute respiratory distress syndrome FXR/Sptlc2 signaling promotes alveolar macrophage mitophagy and limits…

Abstract

Alveolar macrophages (AMs) undergo functional reprogramming that critically regulates lung inflammation. Although mitophagy is essential for mitochondrial quality control, its role in macrophage functional reprogramming during acute respiratory distress syndrome (ARDS) remains unclear. Here, we identify the nuclear receptor Nr1h4 (FXR) as a transcriptional regulator of mitophagy in AMs. FXR activation transcriptionally upregulates serine palmitoyltransferase long chain base subunit 2 (Sptlc2), thereby enhancing mitophagy and promoting an anti-inflammatory macrophage phenotype under inflammatory conditions. The FXR/Sptlc2 axis reduces oxidative stress and inflammatory mediator production while increasing anti-inflammatory markers. Conversely, FXR deficiency impairs mitophagy, exacerbates pulmonary inflammation, and aggravates lung injury in vivo . These findings establish the FXR/Sptlc2 axis as a regulator of mitochondrial quality control and macrophage functional reprogramming and identify it as a potential therapeutic target in ARDS.

BDH1 Attenuates Macrophage Foam Cell Formation and Inflammation in Atherosclerosis Via Modulating Histone H3K9 Acylation Balance and Activating PPAR Signaling.
Yu Wang, Yi Wang, Qinghong Liu +4
Journal of biochemical and molecular toxicology30 Oct 2026Peer-reviewedCC BYFull textImmunologyEurope PMC
SIM2s coordinates programmed mitophagy with respiratory chain supercomplex remodeling during mammary epithelial differentiation
W. W. Porter, R. M. Jenschke, M. Spooner-Harris +7
bioRxiv14 Sep 2026PreprintAll rights reservedFull textCell biologybioRxiv
Inflammatory Subphenotypes for Fluid Management in Acute Respiratory Distress Syndrome: A Subgroup-Level Signal, not an Individual Prescription
Joris Pensier, Emmanuel Lorne
Critical Care Explorations7 Sep 2026Peer-reviewedCC BY 4.0Full textGeneral biologyHAL
Sex-Dependent Microbiome-Metabolome Remodeling Associated with Bacteroides acidifaciens Modulation of Acute Respiratory Distress Syndrome
S. Staley, C. Cooper, S. Oxendine +3
bioRxiv5 Oct 2026PreprintCC BYFull textMicrobiologybioRxiv
Huaban Tongmai decoction attenuates ferroptosis-associated vascular inflammation in carotid artery atherosclerosis with involvement of the p53-Parkin mitophagy pathway
Jiaxi Zou, Jiaxi Zou, Xiujuan Zhou +6
Frontiers in Cell and Developmental Biology6 Nov 2026Peer-reviewedCC BYFull textGeneral biochemistry General biologyDOAJ

Cite

BibTeX RIS

BibTeX

@article{yan2026acute,
  title = {{Acute respiratory distress syndrome FXR/Sptlc2 signaling promotes alveolar macrophage mitophagy and limits lung inflammation}},
  author = {Mi Yan and Yanfei Liu and Mengsheng Deng and Dandan Pi and Jie Zhu and Qinyi Yu and Chun Huang and Qingqi Ran and Wanwei Li and Kun Zhou and Wenjie Peng and Xinyu Duan and Jia Tang and Guangming Yang and Jieqiong Tan and Zhangxue Hu},
  journal = {Cell Reports},
  year = {2026},
  month = oct,
  doi = {10.1016/j.celrep.2026.118175},
  url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124726012544},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Acute respiratory distress syndrome FXR/Sptlc2 signaling promotes alveolar macrophage mitophagy and limits lung inflammation
AU  - Mi Yan
AU  - Yanfei Liu
AU  - Mengsheng Deng
AU  - Dandan Pi
AU  - Jie Zhu
AU  - Qinyi Yu
AU  - Chun Huang
AU  - Qingqi Ran
AU  - Wanwei Li
AU  - Kun Zhou
AU  - Wenjie Peng
AU  - Xinyu Duan
AU  - Jia Tang
AU  - Guangming Yang
AU  - Jieqiong Tan
AU  - Zhangxue Hu
PY  - 2026
DA  - 2026/10/30
JO  - Cell Reports
DO  - 10.1016/j.celrep.2026.118175
UR  - https://linkinghub.elsevier.com/retrieve/pii/S2211124726012544
AB  - Alveolar macrophages (AMs) undergo functional reprogramming that critically regulates lung inflammation. Although mitophagy is essential for mitochondrial quality control, its role in macrophage functional reprogramming during acute respiratory distress syndrome (ARDS) remains unclear. Here, we identify the nuclear receptor Nr1h4 (FXR) as a transcriptional regulator of mitophagy in AMs. FXR activation transcriptionally upregulates serine palmitoyltransferase long chain base subunit 2 (Sptlc2), thereby enhancing mitophagy and promoting an anti-inflammatory macrophage phenotype under inflammatory conditions. The FXR/Sptlc2 axis reduces oxidative stress and inflammatory mediator production while increasing anti-inflammatory markers. Conversely, FXR deficiency impairs mitophagy, exacerbates pulmonary inflammation, and aggravates lung injury in vivo . These findings establish the FXR/Sptlc2 axis as a regulator of mitochondrial quality control and macrophage functional reprogramming and identify it as a potential therapeutic target in ARDS.
SN  - 2211-1247
ER  -

Abstract

Related

Cite