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Nuclear HMGB1 is critical for CD8 T cell IFN-g production and anti-tumor immunity

ABSTRACT: HMGB1 has been extensively studied as a DAMP, with secreted cytokine function. However, its regulation on T cells, especially the function in the nucleus, has not been elucidated. Here, we extracted the total protein of CD8 T cells and enriched the proteins bound to HMGB1 through IP experiment. We found several proteins binding with HMGB1, which suggested that nuclear HMGB1 might regulate the function of CD8 T cells by interacting with these proteins. In our study, we focused on the binding of HMGB1 and Eomes, and found that HMGB1 supported the expression of IFN-g in CD8 T cells by directly regulating the activity of the transcription factor Eomes of IFN-g. In conclusion, we determined the role of nuclear HMGB1 in the differentiation of CD8 T cells and proved that it played an important role in the anti-tumor program of CD8 T cells.

ORGANISM(S): Mus Musculus

SUBMITTER: Kebing Chen

PROVIDER: PXD050639 | iProX | Fri Mar 15 00:00:00 GMT 2024

REPOSITORIES: iProX

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Nuclear HMGB1 is critical for CD8 T cell IFN-γ production and anti-tumor immunity.

Xu Zhiguang Z Ma Weiying W Wang Ji J Chen Haofan H Li Hui H Yin Zhinan Z Hao Jianlei J Chen Kebing K

Cell reports 20240808 8

HMGB1 (high-mobility group box-1) has been extensively studied as a damage-associated molecular pattern, with secreted cytokine function. However, its regulation on T cells, 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 T cells rather than CD4 T cells. Notably, nuclear, but not secreted, HMGB1 supports the expression of IF ...[more]

PMID: 39116204

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