High-mobility group nucleosome binding domain 1 (HMGN1) functions as a Th1-polarizing alarmin.

High-mobility group (HMG) nucleosome binding domain 1 (HMGN1), which previously was thought to function only as a nucleosome-binding protein that regulates chromatin structure, histone modifications, and gene expression, was recently discovered to be an alarmin that contributes extracellularly to the generation of innate and adaptive immune responses. HMGN1 promotes DC recruitment through interacting with a Gαi protein-coupled receptor (GiPCR) and activates DCs predominantly through triggering TLR4. HMGN1 preferentially promotes Th1-type immunity, which makes it relevant for the fields of vaccinology, autoimmunity, and oncoimmunology. Here, we discuss the alarmin properties of HMGN1 and update recent advances on its roles in immunity and potential applications for immunotherapy of tumors.