Deciphering the Role of LIGHT/TNFSF14 in Driving Inflammatory Activity in Human Lung Fibroblasts

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B921
Abstract ID: 4709

Presenting Author:
Nandita Ghosh , Postdoctoral Fellow at La Jolla Inst. for Immunol.

Abstract:

LIGHT/ tumor necrosis factor superfamily member 14 (TNFSF14), is a protein that we previously found was central to lung inflammation and tissue fibrosis in mouse models of severe asthma and systemic sclerosis. We have hypothesized that one of its cellular targets involved in airway remodelling is the lung fibroblast given that both of its receptors, LTβR and HVEM are strongly expressed by these cells. With RNA-seq, we investigated the activity of LIGHT in these cells compared to other important inflammatory cytokines involved in remodeling in lung diseases, namely IL13, IL17A, and TGFβ. LIGHT induced a distinct set of inflammatory gene transcripts in human lung fibroblasts, including the adhesion molecules ICAM-1 and VCAM-1; cytokines IL32, IL33 and IL34; chemokines CXCL1, CXCL5, CXCL6 and CXCL10; and matrix metalloproteinases MMP9 and ADAM8. LIGHT with IL13 synergistically induced CCL2, CCL26, IL32 and ADAM8. LIGHT with IL17A also strongly boosted expression of several chemokines CXCL1, CXCL2, CXCL5, and CXCL6. Lastly, in fibroblasts differentiated into myofibroblasts by TGFβ pre-treatment, LIGHT enhanced the expression of many inflammatory and profibrotic transcripts such as ITGA1, ITGA11, MYH11, and Col1A1. This study highlights the unique as well as synergistic activities of LIGHT on these cells and suggests it could drive strongly inflammatory and remodeling effects in these cells relevant for several diseases dependent on the cytokine environment found in the lungs.