High-mobility group (HMG) proteins are non-histone nuclear proteins that bind nucleosomes and regulate chromosome architecture and gene transcription. Over the past decade, numerous studies have established that some HMG proteins can be released extracellularly and demonstrate distinct extracellular biological activities. Here, we will give a brief overview of HMG proteins and highlight their participation in innate/inflammatory and adaptive immune responses. They have the activities of alarmins, which are endogenous mediators that are rapidly released in response to danger signals initiated by infection and/or tissue damage and are capable of activating innate and adaptive immunity by promoting the recruitment and activation of antigen-presenting cells (APCs).
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