IL-17-producing NKT cells depend exclusively on IL-7 for homeostasis and survival
Natural killer T cells are innate-like T cells that rapidly recognise pathogens and produce cytokines that can shape the ensuing immune response. Recently, IL-17-producing NKT cells have been identified in mice and humans. Studies show that these ROR?t-expressing cells have divergent developmental pathways and functional requirements from other NKT cells, yet the factors that maintain this population in the periphery have not been elucidated. Here we show that NKT17 cells also diverge in their survival requirements. In contrast to conventional NKT cells that are maintained by IL-15, ROR?t+ NKT cells are IL-15 independent and instead rely completely on IL-7. IL-7 initiates a 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 ROR?t 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 correlates with lower SOCS3 levels and high density IL-7 receptor which is greater than most other T lymphocytes. This dependence on IL-7 is also reported for ROR?t+ innate lymphoid cells and CD4+ Th17 cells, and suggests common survival requirements for functionally similar cells.
|Authors||Webster, K. E.; Kim, H. O.; Kyparissoudis, K.; Corpuz, T. M.; Pinget, G. V.; Uldrich, A. P.; Brink, R.; Belz, G. T.; Cho, J. H.; Godfrey, D. I.; Sprent, J.;|
|Responsible Garvan Author|
|Publisher Name||Mucosal Immunology|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/24448098|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/11861|