TNF-alpha and IL-17 synergize to inhibit IL-13 bioactivity via IL-13Ra2 induction in human lung fibroblasts

IL-17 and TNF-alpha synergistically induce surface expression of IL-13Ra2 on primary lung fibroblasts, rendering them unresponsive to IL-13. Neutralizing antibodies to IL-13Ra2 restored IL-13-mediated signaling and transcriptome studies confirmed IL-13Ra2 is an IL-13 decoy receptor. Human fibroblasts were stimulated with IL-13, or stimulated with IL-13 after pre-treatment with TNF-alpha plus IL-17, or stimulated with IL-13 after pre-treatment with TNF-alpha plus IL-17 plus anti-IL13Ra2 antibody. Media and pre-treatment controls are included. 4 replicates per condition: 2 cell passages (biological replicates) each including 2 independent experiments.