A conserved long noncoding RNA, GAPLINC, modulates the immune response during endotoxic shock
Apple Cortez Vollmers, Sergio Covarrubias, Daisy Kuang, Aaron Shulkin, Justin Iwuagwu, Sol Katzman, Ran Song, Kasthuribai Viswanathan, Christopher Vollmers, Edward K. Wakeland, Susan Carpenter
Abstract
Significance Inflammation has largely been studied in the context of protein-coding genes. Recent studies have uncovered lncRNAs as important regulators of immunity. The functional characterization of these genes remains an active area of research. In this study, we identify GAPLINC as a functionally conserved lncRNA between human and mouse. GAPLINC depletion results in enhanced expression of immune response genes that are direct NF-κB targets. Astoundingly, we observe that Gaplinc knockout mice show resistance to LPS-induced endotoxic shock and find that basal expression of inflammatory genes prevents clot formation to protect against multiorgan failure and death. These findings have implications in the treatment of sepsis, in which new therapies targeting lncRNAs can contribute valuable information in understanding inflammation and improving patient outcome.