| First Author | El-Kassar N | Year | 2012 |
| Journal | Int Immunol | Volume | 24 |
| Issue | 10 | Pages | 661-71 |
| PubMed ID | 22899673 | Mgi Jnum | J:187989 |
| Mgi Id | MGI:5438872 | Doi | 10.1093/intimm/dxs067 |
| Citation | El-Kassar N, et al. (2012) High levels of IL-7 cause dysregulation of thymocyte development. Int Immunol 24(10):661-71 |
| abstractText | IL-7 signaling is required for thymocyte development and its loss has a severe deleterious effect on thymus function. Thymocyte-stromal cell interactions and other mechanisms tightly regulate IL-7 expression. We show that disruption of that regulation by over-expression of IL-7 inhibits T-cell development and promotes extensive B-cell lymphopoiesis in the thymus. Our data reveal that high levels of IL-7 negate Notch-1 function in thymocytes found in IL-7 transgenic mice and in co-culture with OP9-DL1 cells. While high levels of IL-7R are present on thymocytes, increased suppressor of cytokine signaling-1 expression blunts IL-7 downstream signaling, resulting in hypo-phosphorylation of proteins in the PI3K-Akt pathway. Consequently, GSK3beta remains active and inhibits Notch-1 signaling as observed by decreased Hes-1 and Deltex expression in thymic progenitors. This is the first demonstration that high levels of IL-7 antagonize Notch-1 signaling and suggest that IL-7 may affect T- versus B-lineage choice in the thymus. |
