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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\u2010induced endoplasmic reticulum (ER) stress. RETREG1\u2010mediated reticulophagy reduces excessive ER stress via the eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) signaling pathway and inhibits membrane\u2010associated RING\u2010CH\u2010type finger 8 (MARCH8)\u2010dependent major histocompatibility complex class II (MHC\u2010II) ubiquitination to maintain antigen presentation in DCs. Consequently,\n                    <jats:italic>\n                      Cd11c\n                      <jats:sup>cre<\/jats:sup>\n                      Retreg1\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    ,\n                    <jats:italic>\n                      Retreg1\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    , and\n                    <jats:italic>\n                      Atf6\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibit impaired DC function, leading to immunosuppression and multiple organ failure in experimental sepsis. Exploration of samples from septic patients, combined with single\u2010cell bioinformatics analysis, further suggests that a deficit in reticulophagy in DCs is associated with the development of human sepsis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511021","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T15:25:41Z","timestamp":1774365941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["RETREG1\u2010Mediated Reticulophagy is Essential for Dendritic Cell Maturation and Function in Sepsis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-4301","authenticated-orcid":false,"given":"Ren\u2010Qi","family":"Yao","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Medical Center of Chinese PLA General Hospital  Beijing China"},{"name":"Medical Innovation Research Division and the Fourth Medical 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