{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T07:10:39Z","timestamp":1793862639916,"version":"4.6.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Septic shock is linked with high mortality and significant long-term morbidity in survivors. However, the specific role of neutrophils in septic shock pathophysiology remains scarce in recent research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood immune cells from healthy donors and patients with septic shock were analyzed using single-cell RNA sequencing and batch RNA sequencing. We measured serum CD121b in both patients and healthy donors. Peripheral immune cells were isolated and exposed to either a CD121b recombinant protein or a CD121b blocking antibody to evaluate the expression of inflammatory factors. Additionally, in a humanized mouse sepsis model, the expression of CD121b in neutrophils across different tissues was assessed following treatment with all-trans retinoic acid (ATRA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study identified a subset of CD10<jats:sup>-<\/jats:sup>CD121b<jats:sup>+<\/jats:sup> neutrophils in the peripheral blood of patients with septic shock. These patients exhibited elevated concentrations of soluble CD121b in serum and urine. Furthermore, outcomes revealed that the presence of CD121b<jats:sup>+<\/jats:sup> neutrophils positively correlated with the severity of septic shock. These cells displayed immunosuppressive characteristics; after blocking CD121b, proinflammatory cytokines increased in peripheral immune cells. Additionally, we found that treatment with ATRA down-regulated the expression of CD121b.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CD121b is closely associated with the progression of septic shock and may serve as a potential predictor indicator of immunosuppression for the condition.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1565797","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T04:30:27Z","timestamp":1743395427000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["CD121b-positive neutrophils predict immunosuppression in septic 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