International immunopharmacology · 2025
RETN stratification identifies a highly immunosuppressive subset of HLA-DRlow monocytes in early stage of polytrauma.
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Luo Jialiu, Zhang Cong, Gu Shuaipeng, Chen Shunyao, Lin Zhiqiang, Tang Tingxuan, Zhang Peidong, Shen Youxie, Chen Deng, Yi Chengla, Dong Liming, Chang Teding, Tang Zhao-Hui
Аннотация
BACKGROUND: Despite early survival, many polytrauma patients ultimately succumb to sepsis driven by trauma-induced immunosuppression. The emergence of HLA-DRlow monocytes was recognized as a biomarker of immunosuppression, yet they are heterogeneous, and reduced HLA-DR expression does not consistently correlate with global monocyte impairment. Therefore, we sought to elucidate the heterogeneity of HLA-DRlow monocytes and clarify their specific contributions to immunosuppression.
METHODS: Single-cell RNA sequencing (scRNA-seq) and Flow cytometry analysis (FCA) were applied to delineate the temporal differentiation trajectories of monocyte subsets post-trauma, leading to the identification of a distinct RETNhighHLA-DRlow monocytes and characterization of its immunosuppressive functions. Finally, we established a clinical cohort and used published datasets to explore its predictive capacity for sepsis in polytrauma patients.
RESULTS: ScRNA-seq and FCA revealed quantitative and functional reprogramming across monocyte subsets and identified a conserved RETNhighHLA-DRlow subset enriched in polytrauma patients, characterized by reduced HLA-DR and elevated RETN expression. This subset exhibited profound impairments in core monocyte functions-including antigen presentation, phagocytosis, and cytokine production-compared to other monocyte subsets. Notably, RETNhighHLA-DRlow monocytes can predict sepsis more accurately than HLA-DRlow monocytes at 72 h (AUC: 0.89 vs. 0.74) post-trauma.
CONCLUSIONS: Our study identified a distinct functional monocyte subset, RETNhighHLA-DRlow monocytes, with markedly impaired hallmark monocyte functions. RETN expression can identify this highly immunosuppressive subset of HLA-DRlow monocytes. In polytrauma patients, RETNhighHLA-DRlow monocytes provided more accurate prediction of sepsis than total HLA-DRlow monocytes.
METHODS: Single-cell RNA sequencing (scRNA-seq) and Flow cytometry analysis (FCA) were applied to delineate the temporal differentiation trajectories of monocyte subsets post-trauma, leading to the identification of a distinct RETNhighHLA-DRlow monocytes and characterization of its immunosuppressive functions. Finally, we established a clinical cohort and used published datasets to explore its predictive capacity for sepsis in polytrauma patients.
RESULTS: ScRNA-seq and FCA revealed quantitative and functional reprogramming across monocyte subsets and identified a conserved RETNhighHLA-DRlow subset enriched in polytrauma patients, characterized by reduced HLA-DR and elevated RETN expression. This subset exhibited profound impairments in core monocyte functions-including antigen presentation, phagocytosis, and cytokine production-compared to other monocyte subsets. Notably, RETNhighHLA-DRlow monocytes can predict sepsis more accurately than HLA-DRlow monocytes at 72 h (AUC: 0.89 vs. 0.74) post-trauma.
CONCLUSIONS: Our study identified a distinct functional monocyte subset, RETNhighHLA-DRlow monocytes, with markedly impaired hallmark monocyte functions. RETN expression can identify this highly immunosuppressive subset of HLA-DRlow monocytes. In polytrauma patients, RETNhighHLA-DRlow monocytes provided more accurate prediction of sepsis than total HLA-DRlow monocytes.