IL-17-producing NKT cells depend exclusively on IL-7 for homeostasis and survival
- Author(s)
- Webster, KE; Kim, HO; Kyparissoudis, K; Corpuz, TM; Pinget, GV; Uldrich, AP; Brink, R; Belz, GT; Cho, JH; Godfrey, DI; Sprent, J;
- Details
- Publication Year 2014-01-22,Volume 7,Issue #5,Page 1058-1067
- Journal Title
- Mucosal immunology
- Publication Type
- Journal Article
- Abstract
- Natural killer T (NKT) cells are innate-like T cells that rapidly recognize pathogens and produce cytokines that shape the ensuing immune response. IL-17-producing NKT cells are enriched in barrier tissues, such as the lung, skin, and peripheral lymph nodes, and the factors that maintain this population in the periphery have not been elucidated. Here we show that NKT17 cells deviate from other NKT cells in their survival requirements. In contrast to conventional NKT cells that are maintained by IL-15, RORgammat+ NKT cells are IL-15 independent and instead rely completely on IL-7. IL-7 initiates a T-cell receptor-independent (TCR-independent) expansion of NKT17 cells, thus supporting their homeostasis. Without IL-7, survival is dramatically impaired, yet residual cells remain lineage committed with no downregulation of RORgammat evident. Their preferential response to IL-7 does not reflect enhanced signaling through STAT proteins, but instead is modulated via the PI3K/AKT/mTOR signaling pathway. The ability to compete for IL-7 is dependent on high-density IL-7 receptor expression, which would promote uptake of low levels of IL-7 produced in the non-lymphoid sites of lung and skin. This dependence on IL-7 is also reported for RORgammat+ innate lymphoid cells and CD4+ Th17 cells, and suggests common survival requirements for functionally similar cells.Mucosal Immunology advance online publication, 22 January 2014; doi:10.1038/mi.2013.122.
- Publisher
- NPG
- Research Division(s)
- Molecular Immunology
- Publisher's Version
- https://doi.org/10.1038/mi.2013.122
- NHMRC Grants
- NHMRC/1047903,
- Terms of Use/Rights Notice
- © 2014 Society for Mucosal Immunology
Creation Date: 2014-04-16 08:43:45