| First Author | Kamimura D | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 8 | Pages | 5433-41 |
| PubMed ID | 18832700 | Mgi Jnum | J:140764 |
| Mgi Id | MGI:3814515 | Doi | 10.4049/jimmunol.181.8.5433 |
| Citation | Kamimura D, et al. (2008) Endoplasmic reticulum stress regulator XBP-1 contributes to effector CD8+ T cell differentiation during acute infection. J Immunol 181(8):5433-41 |
| abstractText | The transcription factor X-box-binding protein-1 (XBP-1) plays an essential role in activating the unfolded protein response in the endoplasmic reticulum (ER). Transcribed XBP-1 mRNA is converted to its active form by unconventional cytoplasmic splicing mediated by inositol-requiring enzyme-1 (IRE-1) upon ER stress. We report activation of the IRE-1/XBP-1 pathway in effector CD8(+) T cells during the response to acute infection. Transcription of unspliced XBP-1 mRNA is up-regulated by IL-2 signals, while its splicing is induced after TCR ligation. Splicing of XBP-1 mRNA was evident during the expansion of Ag-specific CD8(+) T cells in response to viral or bacterial infection. An XBP-1 splicing reporter revealed that splicing activity was enriched in terminal effector cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1). Overexpression of the spliced form of XBP-1 in CD8(+) T cells enhanced KLRG1 expression during infection, whereas XBP-1(-/-) CD8(+) T cells or cells expressing a dominant-negative form of XBP-1 showed a decreased proportion of KLRG1(high) effector cells. These results suggest that, in the response to pathogen, activation of ER stress sensors and XBP-1 splicing contribute to the differentiation of end-stage effector CD8(+) T cells. |
