DataVXAdvanced SciencePaper
journal article·2026-05Open access

RETREG1‐Mediated Reticulophagy is Essential for Dendritic Cell Maturation and Function in Sepsis

Ren‐Qi Yao, Chao Ren, Li‐Yu Zheng, Jing‐Yan Li, Wen‐Feng Wu, Yu‐Xuan Li, Li‐Xue Wang, Yu Duan, Lu Wang, Shuang‐Qing Liu, Peng‐Yi He, Peng‐Yue Zhao, Sen Tong, Zhi‐Xuan Li, Tuo Zhang, Meng‐Yao Wu, Shu‐Ting Wei, Ning Dong, Yao Wu, Hui Zhang, Xiao‐Mei Zhu, Zi‐Cheng Zhang, Guo‐Sheng Wu, Zhao‐Fan Xia, Xiao‐Hui Du, Hong‐Jun Kang, Zui Zou, Dao‐Lin Tang, Yong‐Ming Yao

Advanced Science· Volume 13· Issue 29
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Source abstract

Abstract

ABSTRACT Dendritic cells (DCs) are crucial antigen‐presenting cells that mediate the interplay between innate and adaptive immunity during lethal infections. Here, we report the key role of reticulophagy regulator 1 (RETREG1), a selective autophagy receptor, in maintaining DC maturation and function in the early stage of sepsis. Mechanistically, activating transcription factor 6 (ATF6) acts as a direct transcription factor regulating RETREG1 expression in response to bacterial lipopolysaccharide‐induced endoplasmic reticulum (ER) stress. RETREG1‐mediated reticulophagy reduces excessive ER stress via the eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) signaling pathway and inhibits membrane‐associated RING‐CH‐type finger 8 (MARCH8)‐dependent major histocompatibility complex class II (MHC‐II) ubiquitination to maintain antigen presentation in DCs. Consequently, Cd11c cre Retreg1 fl/fl , Retreg1 −/− , and Atf6 −/− mice exhibit impaired DC function, leading to immunosuppression and multiple organ failure in experimental sepsis. Exploration of samples from septic patients, combined with single‐cell bioinformatics analysis, further suggests that a deficit in reticulophagy in DCs is associated with the development of human sepsis.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Autophagy in Disease and Therapy · Endoplasmic Reticulum Stress and Disease · Ferroptosis and cancer prognosis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of General Surgery The First Medical Center of Chinese PLA General Hospital Beijing China

Medical Innovation Research Division and the Fourth Medical Center of Chinese PLA General Hospital Beijing China

Department of Pulmonary and Critical Care Medicine Beijing Chaoyang Hospital Capital Medical University Beijing China

Department of Emergency The Second Hospital of Hebei Medical University Shijiazhuang China

Department of Plastic and Reconstructive Surgery Zhongshan Hospital and Shanghai Geriatric Medical Center Fudan University Shanghai China

Department of Breast Surgery The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou China

Department of Critical Care Medicine The First People's Hospital of Chenzhou Southern Medical University Chenzhou China

Department of Critical Care Medicine The First Medical Center of Chinese PLA General Hospital Beijing China

Department of Orthopedics The Fourth Medical Center of Chinese PLA General Hospital Beijing China

Department of Burn Surgery The First Affiliated Hospital of Naval Medical University Shanghai China

Faculty of Anesthesiology Changhai Hospital Naval Medical University Shanghai China

School of Anesthesiology Naval Medical University Shanghai China

Center For DAMP Biology Department of Surgery UT Southwestern Medical Center Dallas Texas USA

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China · Natural Science Foundation of Beijing Municipality

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