Zheng Li; Meng Wu; Xuesong Yan; Xin Feng; Ye Chen & Ming Meng

This study investigates the role of invariant natural killer T (iNKT) cells in pulmonary fibrosis using C57BL/6 wild-type (WT) and Ja18-/- knockout (KO) mice. KO mice exhibited accelerated fibrosis progression, marked by significant weight loss, elevated lung wet weight, and increased hydroxyproline content compared to WT mice. Histopathological analysis revealed earlier inflammatory cell infiltration (day 14 vs. later in WT) and pronounced collagen deposition in KO mice, alongside upregulated fibrosis- related biomarkers (TGF-β1 and α-SMA) via Western blot. Flow cytometry demonstrated complete iNKT cell absence in KO mice and reduced total macrophages, with skewed M1/M2 macrophage polarization. These findings suggest iNKT cell deficiency exacerbates pulmonary fibrosis by disrupting macrophage homeostasis. The study proposes that iNKT cells modulate fibrosis through macrophage regulation, potentially influencing pro-fibrotic cytokine production and collagen synthesis. This highlights iNKT cells as critical regulators in idiopathic pulmonary fibrosis (IPF) pathogenesis and positions iNKT-based immunotherapy as a novel therapeutic strategy to restore immune balance and mitigate fibrotic progression. Further research should explore mechanistic links between iNKT cells, macrophage subsets, and downstream fibrotic pathways to validate these targets for clinical translation in IPF treatment.

KEY WORDS: Pulmonary fibrosis; Natural killer T-Cells; Transforming growth factor Beta1; Immunotherapy.

LI, Z.; WU, M.; YAN, X.; FENG, X.; CHEN, Y. & MENG, M. Effect of iNKT cell deficiency on pulmonary fibrosis formation in mice. Int. J. Morphol., 44(3):894-902, 2026.