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Targeted immunotherapy rescues pulmonary fibrosis by against activated fibroblasts and regulating alveolar cell profile

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a severe lung disease in the world, but has limited clinical therapies. Fibrosis maintains dynamic balance with overactivated fibroblasts. Given pulmonary cell regeneration, the lung may have self-repairing ability if fibrosis is removed by clearance of overactivated fibroblasts. The aim of the study is to evaluate therapeutic activity of transient CAR-T cells generated via a novelly designed LNP-mRNA system and address the relevant mechanism to epithelial cell polarization in a mouse model of bleomycin-induced IPF. Studies on proteomes and histology showed that fibrosis-induced ECM stiffening impaired epithelial cell polarization that limited cell’s self-healing ability. The proposed LNP-mRNA therapy eliminated overactivated fibroblasts and removed pulmonary fibrosis successfully. The decreased ECM stiffness and the improvement of extracellular environment facilitated re-establishment of cell polarity and restored the self-repairing ability of epithelial cell. Hence, LNP-mRNA treatment for IPF can recover pulmonary structure and function close to a healthy lung. This therapy shows a potential treatment for IPF patients.

INSTRUMENT(S): Orbitrap Astral

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung, Epithelial Cell

DISEASE(S): Pulmonary Fibrosis

SUBMITTER: Jing Yan

LAB HEAD: Yunlong Huo

PROVIDER: PXD053333 | Pride | 2025-03-19

REPOSITORIES: Pride

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	A1-D0.raw	Raw
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	A5-D0.raw	Raw
	B10-IPF-D28.raw	Raw

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