Other
11 Authors
- He J,
- Spolski R,
- Andraski AB,
- Kelsall BL,
- West EE,
- Li P,
- Wan CK,
- Oh J,
- Leonard WJ,
- Wong EA,
- Yu ZX
| First Author | Wan CK | Year | 2013 |
| Journal | Immunity | Volume | 38 |
| Issue | 3 | Pages | 514-27 |
| PubMed ID | 23453633 | Mgi Jnum | J:194831 |
| Mgi Id | MGI:5474888 | Doi | 10.1016/j.immuni.2013.02.011 |
| Citation | Wan CK, et al. (2013) The Cytokines IL-21 and GM-CSF Have Opposing Regulatory Roles in the Apoptosis of Conventional Dendritic Cells. Immunity 38(3):514-27 |
| abstractText | Interleukin-21 (IL-21) has broad actions on T and B cells, but its actions in innate immunity are poorly understood. Here we show that IL-21 induced apoptosis of conventional dendritic cells (cDCs) via STAT3 and Bim, and this was inhibited by granulocyte-macrophage colony-stimulating factor (GM-CSF). ChIP-Seq analysis revealed genome-wide binding competition between GM-CSF-induced STAT5 and IL-21-induced STAT3. Expression of IL-21 in vivo decreased cDC numbers, and this was prevented by GM-CSF. Moreover, repetitive alpha-galactosylceramide injection of mice induced IL-21 but decreased GM-CSF production by natural killer T (NKT) cells, correlating with decreased cDC numbers. Furthermore, adoptive transfer of wild-type CD4(+) T cells caused more severe colitis with increased DCs and interferon-gamma (IFN-gamma)-producing CD4(+) T cells in Il21r(-/-)Rag2(-/-) mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2(-/-) mice. Thus, IL-21 and GM-CSF exhibit cross-regulatory actions on gene regulation and apoptosis, regulating cDC numbers and thereby the magnitude of the immune response. |
