Fig. 6. Inhibition of immune checkpoints together with IL-6 resolves lung fibrosis.

a Whole-lung scaffold map for Bleomycin-induced lung fibrosis in mice. Each node represents unsupervised cell clusters. b Representative mass cytometry plot demonstrating increased expression of immune-checkpoint proteins-CD47⁺ PD-L1⁺ in fibroblasts, an expansion of CD11b⁺ F4/80⁺ macrophages, regulator T cells (CD3⁺ CD4⁺ CD25⁺ FOXP3⁺) and exhausted T cells (CD3⁺ CD8⁺ PD-1⁺ TIM3⁺) in mouse model after fibrosis induction with bleomycin for 2 weeks. c, d Representative images of Micro CT scans of wildtype and B6.129S2-Il6^tm1Kopf/J (IL-6KO) mice highlighting increased fibrosis in the lung after fibrosis induction (wildtype and IL-6KO mice) and much improved fibrosis after treatment with HAC (anti-PD-L1) alone or combined with a blocking antibody against CD47 or/and IL-6. Data are expressed as mean ± SD of five animals and analyzed by using one-way ANOVA followed by Tukey’s multiple comparisons test for multiple comparison. n.s. non-significant; *P < 0.05; ****P < 0.0001. e Trichrome of lung sections of control mice, mice after fibrosis induction with bleomycin (wildtype and IL-6KO mice) and mice after treatment with blocking antibodies against IL-6 and CD47 and HAC (the blocking reagent against PD-L1) demonstrating markedly improved fibrosis (significantly decreased blue stained areas on Masson’s trichrome stain which correspond to cross-linked collagen) and diminished PD-L1 expression in FSP1⁺ fibroblasts after treatment. Scale bar, 100 μm. See Supplementary Data 2 for statistical details. Source data are provided as a Source Data file.