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Immunostimulation Pathways of Extracellular Nucleosomes

Huawei Wang, Chuanzheng Zhou

Circulating nucleosomes released from dying or damaged cells have been observed to be associated with in-flammation and autoimmune diseases, indicating that extracellular nucleosomes have immunostimulation. Early studies have demonstrated that extracellular nucleosomes can induce immune responses in a TLR9-dependent mechanism. A very recent study reported that extracellular nucleosomes can be taken up by mammalian cells. After cellular uptake, nucleosomes bind and activate cGAS in the cytoplasm, inducing the expression and secre-tion of type I interferons and proinflammatory cytokines. Thus, the cGAS-dependent mechanism represents a new pathway for the immunostimulation of extracellular nucleosomes.