| First Author | Xu T | Year | 2021 |
| Journal | J Immunol | Volume | 206 |
| Issue | 9 | Pages | 2170-2183 |
| PubMed ID | 33863789 | Mgi Jnum | J:320460 |
| Mgi Id | MGI:6727241 | Doi | 10.4049/jimmunol.2001459 |
| Citation | Xu T, et al. (2021) Kdm6b Regulates the Generation of Effector CD8(+) T Cells by Inducing Chromatin Accessibility in Effector-Associated Genes. J Immunol 206(9):2170-2183 |
| abstractText | The transcriptional and epigenetic regulation of CD8(+) T cell differentiation is critical for balancing pathogen eradication and long-term immunity by effector and memory CTLs, respectively. In this study, we demonstrate that the lysine demethylase 6b (Kdm6b) is essential for the proper generation and function of effector CD8(+) T cells during acute infection and tumor eradication. We found that cells lacking Kdm6b (by either T cell-specific knockout mice or knockdown using short hairpin RNA strategies) show an enhanced generation of memory precursor and early effector cells upon acute viral infection in a cell-intrinsic manner. We also demonstrate that Kdm6b is indispensable for proper effector functions and tumor protection, and that memory CD8(+) T cells lacking Kdm6b displayed a defective recall response. Mechanistically, we identified that Kdm6b, through induction of chromatin accessibility in key effector-associated gene loci, allows for the proper generation of effector CTLs. Our results pinpoint the essential function of Kdm6b in allowing chromatin accessibility in effector-associated genes, and identify Kdm6b as a potential target for therapeutics in diseases with dysregulated effector responses. |
