Published online Aug 26, 2026. doi: 10.4252/wjsc.121124
Revised: May 12, 2026
Accepted: June 22, 2026
Published online: August 26, 2026
Processing time: 131 Days and 22.2 Hours
Sepsis-associated acute respiratory distress syndrome (ARDS) is characterized by diffuse alveolar epithelial injury, dysregulated immune activation, and impaired inflammation resolution. Alveolar epithelial stem/progenitor cells are critical for restoring alveolar integrity; however, their phenotypic changes and association with local and systemic immune microenvironments remain insufficiently defined.
To investigate the relationship between phenotypic changes in alveolar epithelial stem cells/progenitor cells and the immune microenvironment imbalance in sepsis-associated ARDS and evaluate its correlation with the severity of the disease and intensive care unit (ICU) outcomes and to provide a basis for individualized intervention based on epithelial repair and immune regulation.
A total of 200 patients with sepsis-ARDS who were admitted to the ICU of Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, from January 2023 to December 2025, were retrospectively included. They were divided into a moderate group (n = 111) and a severe group (n = 89) according to Berlin’s criteria. Bronchoalveolar lavage fluid (BALF) and peripheral blood were collected within 48 hours after tracheal intubation. Quantitative polymerase chain reaction was used to detect the relative expression of alveolar epithelial type II cells progenitor cell marker surfactant protein C (SFTPC) in BALF cell pellets, and the proportion of epithelial cell adhesion molecule and CD44-positive cells was determined by flow cytometry. The T helper 17 cells (Th17)/regulatory T cells (Treg) ratio in BALF, the ratio of CD4+/CD8+ T cells, and plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-10 were detected simultaneously. Blood lactate, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2), sequential organ failure assessment (SOFA)/acute physiology and chronic health evaluation II scores, and duration of mechanical ventilation, ICU stay, and 28-day mortality were recorded.
In the severe group, SOFA, acute physiology and chronic health evaluation II, and lactic acid levels significantly increased, whereas PaO2/FiO2 decreased (all P < 0.001). Compared with the moderate group, the severe group had significantly decreased SFTPC and epithelial cell adhesion molecule, and increased CD44 (P < 0.001); the Th17/Treg ratio was increased, but the proportion of CD4+ T cells was decreased, and the proportion of CD8+ T cells was increased. IL-6 and tumor necrosis factor-α were significantly increased (P < 0.05). Correlation analysis showed that SFTPC was negatively correlated with Th17/Treg, IL-6, and lactic acid levels and positive correlated with PaO2/FiO2 (r = 0.510, P < 0.001). Multivariate logistic regression analysis indicated that SOFA (odds ratio = 1.33, P = 0.005) and SFTPC (odds ratio = 0.03, P = 0.002) were independent predictors of 28-day mortality.
The phenotypic decline of alveolar epithelial type II cells progenitor cells in sepsis-ARDS is associated with an imbalance in T cell subsets and increased levels of inflammatory factors, which are also closely related to oxygenation disorders and adverse outcomes. Epithelial repair-related indicators such as SFTPC can be used for risk stratification and suggest potential avenues for translational intervention.
Core Tip: In sepsis-acute respiratory distress syndrome, the downregulation of alveolar epithelial type II cells progenitor markers (surfactant protein C, epithelial cell adhesion molecule) is accompanied by T-cell subset imbalance and elevated proinflammatory cytokines, which are closely associated with disease severity, oxygenation impairment and increased lactate; surfactant protein C and sequential organ failure assessment score are independent predictors of 28-day mortality, suggesting that stem/progenitor cell-mediated immune microenvironment remodeling may serve as a promising prognostic indicator and therapeutic target for sepsis-acute respiratory distress syndrome.