Fig 2: sh-Chi3l1-MSCs promote IL-17A production in aGvHD mice. (a, b) Lymphocytes were obtained from the spleens of aGvHD mice on day 14 after hUC-MSC, sh-Chi3l1-MSC, sh-NC-MSC (1 × 106), or PBS (0.2 ml) treatment. Intracellular cytokines in lymphocytes were measured by flow cytometry. (a) IFN-γ and IL-17A were analyzed by flow cytometry. (b) The proportion of intracellular cytokines IFN-γ and IL-17A was measured in different groups. (c) Serum IFN-γ and IL-17A were measured by ELISA (n = 8, three independent experiments, one-way ANOVA, and Tukey's multiple comparison test, ∗P < 0.05; ∗∗P < 0.01; ns: not significant). IFN-γ: interferon-gamma; IL-17A: interleukine-17A.

Fig 3: Positive association of CHI3L1 expression with lymphangiogenesis. (a) Enrichment plots from gene set enrichment analysis results reveal the ‘Lymph_Angiogenesis’ pathway enriched in urothelial carcinoma of the bladder (UCB) patients with high CHI3L1 expression in the TCGA‐BLCA cohort. (b) Heatmap displaying the core enrichment genes of the lymphangiogenesis pathway and their expression to CHI3L1 in the TCGA‐BLCA cohort. (c) Results of qRT‐PCR assay illustrating the mRNA expression of CHI3L1, VEGFC, PDGFB and VEGFA in our patients (n = 12). (d) Representative images of four‐colour immunofluorescence staining, showing CHI3L1 (red), the lymphatic endothelium marker (D2‐40, green), the vascular endothelium marker (CD105, yellow) and the cytokeratin marker (CK, white), with counterstaining using 4′,6‐diamidino‐2‐phenylindole (DAPI, blue). Scale bars, 50 μm. (e, f) Scatter plots indicate the associations of CHI3L1+ stromal cells with lymphatic vessel density (LVD) (e) or micro‐vessel density (MVD) (f) in UCB tissues. In the correlation analysis between CHI3L1+ stromal cells and MVD, there are two cases of overlapped data, marked with red arrows. A significance level of P < 0.05 was considered statistically significant. Statistical significance was determined by the unpaired t‐test and is indicated by P‐values. ***P < 0.001.

Fig 4: The differential expression analysis of baseline tumour samples. a Differential expression between the response group and the non-response group in baseline tumour samples. b CHI3L1 expression in baseline tumour samples showed a better predictive ability to treatment response than PD-L1. c The difference in OS between high and low CHI3L1 IHC scores in baseline tumour samples. d The difference in PFS between high and low CHI3L1 IHC scores in baseline tumour samples. e CHI3L1 IHC expression comparison in baseline tumour samples between non-response and response groups. f Representative IHC images for CHI3L1 in different response groups

Fig 5: CNV area, YKL‐40, and phosphorylated protein level of ERK1/2 pathway are decreased after intravitreal injection of the anti‐YKL‐40 antibody. (A) The HE staining results showed mouse retina structures and the areas of CNV after intravitreal injection of the anti‐YKL‐40 antibody or PBS solution postlaser photocoagulation. Scale bar = 50 μm. (B–E) The protein levels of YKL‐40, VEGF, and phosphorylated ERK1/2 in the RPE/choroid complex of the mice after intravitreal injection of anti‐YKL‐40 antibody or PBS solution postlaser photocoagulation. (Mean ± SEM; n = 4; one‐way ANOVA with Bonferroni correction). P < 0.05 denotes statistical significance, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.