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Updated: Mar 7, 2026
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Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
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RETREG1/FAM134B-mediated ERGICphagy regulates GSDME-dependent dendritic cell pyroptosis during sepsis
Yu Duan1,2,3, Peng-Yi He2, Cheng-Long Zhu4
1Institute of Critical Care Medicine, the First People's Hospital of Chenzhou, The First Affiliated Hospital of Xiangnan University, Chenzhou, China.
Autophagy
|March 6, 2026
Summary
Reticulophagy regulator 1 (RETREG1) protects against sepsis-induced immune dysfunction by preventing dendritic cell pyroptosis. Upregulating RETREG1 may offer a therapeutic strategy for sepsis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Medicine
Background:
- Sepsis causes dendritic cell (DC) pyroptosis, leading to immune dysfunction.
- Mechanisms regulating DC pyroptosis in sepsis are not fully understood.
- RETREG1/FAM134B is implicated in programmed cell death and cell viability.
Purpose of the Study:
- Investigate the role of RETREG1 in DC death during sepsis.
- Elucidate the regulatory pathways of RETREG1 in sepsis-induced DC pyroptosis.
Main Methods:
- Assessed RETREG1 expression in DCs during septic challenge.
- Depleted RETREG1 in DCs to evaluate its effect on pyroptosis and immune function.
- Investigated the involvement of CASP3-GSDME and STING1 signaling pathways.
- Examined the impact of Tmed9 downregulation on ERGIC structure and pyroptosis.
Main Results:
- RETREG1 upregulation correlated with preserved immune function during sepsis.
- RETREG1 depletion exacerbated DC pyroptosis and immune dysfunction via CASP3-GSDME activation.
- Defective RETREG1 impaired ERGIC degradation, activating STING1 and promoting pyroptosis.
- Downregulating Tmed9 disrupted ERGIC, inhibiting STING1 and GSDME-mediated pyroptosis.
Conclusions:
- RETREG1 plays a protective role against DC pyroptosis and immune suppression in sepsis.
- The RETREG1 pathway involves regulating ERGIC degradation and STING1 activation.
- Modulating RETREG1 presents a potential therapeutic approach for sepsis-induced immune impairment.
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