Lymphotoxin Beta Receptor Activity in Fibroblasts Regulates Collagen Synthesis and is Crucial for Lung Fibrosis

Fibroblast-specific deletion of LTßR in mice exposed to allergen significantly reduces lung collagen deposition and inflammation, despite unchanged fibroblast numbers. LIGHT-LTßR signaling in human pulmonary fibroblasts increases the expression of multiple collagen isoforms, molecules involved in structural rigidity, and molecules controlling cell migration and adhesion, explaining the importance of LTßR in promoting lung fibrosis. Overall design: Bulk RNA seq. analysis from human pulmonary fibroblasts stimulated with 50 ng/ml LIGHT, 5 ng/ml TGFß, 25 ng/ml IL-13, and 100 ng/ml IL-17A and in combination of IL13 or IL17A with LIGHT