Abstract
HMGB1 (high-mobility group box-1) has been extensively studied as a damage-associated molecular pattern, with secreted cytokine function. However, its regulation on Tcells, especially the function in the nucleus, has not been elucidated. Here, we use conditional knockout (HMGB1-f/f; CD2-cre) mice and find that HMGB1 potentiates the proliferation and interferon gamma (IFN-γ) expression of CD8 Tcells rather than CD4 Tcells. Notably, nuclear, but not secreted, HMGB1 supports the expression of IFN-γ in CD8 Tcells via directly regulating the activity of Eomes, the transcription factor for IFN-γ. Functional study shows that HMGB1 promotes the anti-tumor ability of CD8 Tcells invitro and invivo. Finally, tumor environmental interleukin-7 promotes HMGB1 and IFN-γ production via fatty acid oxidation in CD8 Tcells. Overall, we identify the role of nuclear HMGB1 in CD8 Tcell differentiation and demonstrate that it plays an important role in the anti-tumor programs of CD8 Tcells.
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