The STAT3-Binding Long Noncoding RNA lnc-DC Controls Human Dendritic Cell Differentiation

TLDR

Long noncoding RNAs are key regulators in biology, yet few are known to control immune cell differentiation. lnc‑DC binds STAT3 in the cytoplasm, blocking SHP1 interaction and thereby promoting STAT3 phosphorylation at Tyr705. lnc‑DC is uniquely expressed in human conventional dendritic cells; its loss impairs DC differentiation and T‑cell activation by activating STAT3, revealing a novel lncRNA regulator of dendritic cell development.

Abstract

Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes; however, few have been identified that regulate immune cell differentiation and function. Here, we identified lnc-DC, which was exclusively expressed in human conventional dendritic cells (DCs). Knockdown of lnc-DC impaired DC differentiation from human monocytes in vitro and from mouse bone marrow cells in vivo and reduced capacity of DCs to stimulate T cell activation. lnc-DC mediated these effects by activating the transcription factor STAT3 (signal transducer and activator of transcription 3). lnc-DC bound directly to STAT3 in the cytoplasm, which promoted STAT3 phosphorylation on tyrosine-705 by preventing STAT3 binding to and dephosphorylation by SHP1. Our work identifies a lncRNA that regulates DC differentiation and also broadens the known mechanisms of lncRNA action.