CD70 Activation Decreases Pulmonary Fibroblast Production of Extracellular Matrix Proteins.

CD70 Activation Decreases Pulmonary Fibroblast Production of Extracellular Matrix Proteins. Am J Respir Cell Mol Biol. 2020 Apr 22;: Authors: Tran-Nguyen TK, Xue J, Feghali-Bostwick C, Sciurba FC, Kass DJ, Duncan SR Abstract Idiopathic pulmonary fibrosis (IPF) is a lethal, medically refractory syndrome characterized by intrapulmonary accumulations of extracellular matrix (ECM) proteins produced by fibroblasts. Activation, clonal expansions, and differentiation of lymphocytes are also frequently present in IPF. Activated T-cells are known to exert several effects that promote ECM production, but opposing homeostatic actions, wherein T-cells can inhibit fibrosis, are less well understood. We found CD27, a TNF receptor ubiquitously expressed on naïve T-cells, is downregulated on CD4 T-cells of IPF patients and CD70, the sole ligand for CD27, is present on human pulmonary fibroblasts. We hypothesized cognate engagements between lymphocyte CD27 and fibroblast CD70 could have functional consequences. Accordingly, a series of subsequent studies were conducted to examine the possible role of CD27-CD70 interactions in the regulation of fibrogenesis. Using immunoblotting, flow cytometry, RT-PCR, and kinomic assays, we found fibroblast CD70 expression was inversely correlated with cell density, and upregulated by TGF-β1. CD70 agonists, including T-cell-derived soluble CD27, markedly diminished fibroblast collagen and fibronectin synthesis, an...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research