CD121b-positive neutrophils predict immunosuppression in septic shock.

BACKGROUND: 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. METHODS: 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). RESULTS: This study identified a subset of CD10(-)CD121b(+) 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(+) 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. CONCLUSIONS: CD121b is closely associated with the progression of septic shock and may serve as a potential predictor indicator of immunosuppression for the condition.