Fig. 7. PLET1 is present in patients with human IAV-induced ARDS and rPlet1 administration protects lung epithelial barrier function and rescues mice after lethal IAV infection.

a Soluble PLET1 and b total protein concentration in BALF of patients with IAV-induced ARDS (n = 14) or healthy patients (n = 8) (patient characteristics provided in Supplementary Table) (**p = 0.0075, ***p = 0.0005). c PLET1 concentration was negatively correlated with total protein concentration (n = 14). d Schematic representation of the experiments conducted in (e)–(i), rPlet1 (5 µg; squares) or PBS (circles) were applied intratracheally (i.t.) at D3 p.i. The figure was created with BioRender. e Lung histological sections of IAV-infected mice stained with H&E at D7 p.i. Bottom images underneath are magnifications of the top images (red squares); scale bars represent 100 µm (top) and 50 µm (bottom). f Percentage of Annexin V⁺ AECs (n = 6) (**p = 0.0011). g mRNA expression (qPCR) of tight junction component genes in flow-sorted EpCam⁺ cells (n = 3) (*p = 0.0046, ****p < 0.0001). h Quantification of barrier dysfunction by FITC-Albumin fluorescence analysis in BALF (n = 6) (**p = 0.002). i Ki67⁺ percentage of AEC II indicating proliferation (n = 6) (***p = 0.0003). j Survival of IAV-infected mice (5 × 10² pfu) treated with PBS or rPlet1 at D3 p.i. (n = 9/group in two separate experiments) (***p = 0.0001). k Schematic summary: CD206⁺ BMDM2- and BMDM2-derived TR-AM express Plet1 driving AEC II proliferation and upregulation of tight junction genes, ultimately resulting in AEC barrier repair. Application of exogenous, recombinant Plet1 reproduces these effects, highlighting its therapeutic potential. The figure was created with BioRender. Data are representative of three independent experiments showing mean ± SEM. Significance was calculated using two-sided Student’s t-test on (a) (Welch’s correction), (b) (Welch’s correction), (f, h, i) (Welch’s correction), Spearman’s rank correlation test in (c), Log-rank (Mantel–Cox) test in (j), (g) two-way ANOVA (followed by Šídák’s test). AEC alveolar epithelial cell, BALF bronchoalveolar lavage fluid, D day. Panel (k) was generated by BioRender. Source data are provided as a Source Data file.