| First Author | Neubert EN | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 5631 |
| PubMed ID | 37704621 | Mgi Jnum | J:340557 |
| Mgi Id | MGI:7527910 | Doi | 10.1038/s41467-023-41352-0 |
| Citation | Neubert EN, et al. (2023) HMGB2 regulates the differentiation and stemness of exhausted CD8(+) T cells during chronic viral infection and cancer. Nat Commun 14(1):5631 |
| abstractText | Chronic infections and cancers evade the host immune system through mechanisms that induce T cell exhaustion. The heterogeneity within the exhausted CD8(+) T cell pool has revealed the importance of stem-like progenitor (Tpex) and terminal (Tex) exhausted T cells, although the mechanisms underlying their development are not fully known. Here we report High Mobility Group Box 2 (HMGB2) protein expression is upregulated and sustained in exhausted CD8(+) T cells, and HMGB2 expression is critical for their differentiation. Through epigenetic and transcriptional programming, we identify HMGB2 as a cell-intrinsic regulator of the differentiation and maintenance of Tpex cells during chronic viral infection and in tumors. Despite Hmgb2(-/-) CD8(+) T cells expressing TCF-1 and TOX, these master regulators were unable to sustain Tpex differentiation and long-term survival during persistent antigen. Furthermore, HMGB2 also had a cell-intrinsic function in the differentiation and function of memory CD8(+) T cells after acute viral infection. Our findings show that HMGB2 is a key regulator of CD8(+) T cells and may be an important molecular target for future T cell-based immunotherapies. |
