| First Author | Golec DP | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 8 | Pages | 2421-2435 |
| PubMed ID | 28652304 | Mgi Jnum | J:244235 |
| Mgi Id | MGI:5913014 | Doi | 10.1084/jem.20170844 |
| Citation | Golec DP, et al. (2017) Thymic progenitors of TCRalphabeta+ CD8alphaalpha intestinal intraepithelial lymphocytes require RasGRP1 for development. J Exp Med 214(8):2421-2435 |
| abstractText | Strong T cell receptor (TCR) signaling largely induces cell death during thymocyte development, whereas weak TCR signals induce positive selection. However, some T cell lineages require strong TCR signals for differentiation through a process termed agonist selection. The signaling relationships that underlie these three fates are unknown. RasGRP1 is a Ras activator required to transmit weak TCR signals leading to positive selection. Here, we report that, despite being dispensable for thymocyte clonal deletion, RasGRP1 is critical for agonist selection of TCRalphabeta+CD8alphaalpha intraepithelial lymphocyte (IEL) progenitors (IELps), even though both outcomes require strong TCR signaling. Bim deficiency rescued IELp development in RasGRP1-/- mice, suggesting that RasGRP1 functions to promote survival during IELp generation. Additionally, expression of CD122 and the adhesion molecules alpha4beta7 and CD103 define distinct IELp subsets with differing abilities to generate TCRalphabeta+CD8alphaalpha IEL in vivo. These findings demonstrate that RasGRP1-dependent signaling underpins thymic selection processes induced by both weak and strong TCR signals and is differentially required for fate decisions derived from a strong TCR stimulus. |
