dc.contributor.author | Wu, Chuan | en_US |
dc.contributor.author | Yosef, Nir | en_US |
dc.contributor.author | Thalhamer, Theresa | en_US |
dc.contributor.author | Zhu, Chen | en_US |
dc.contributor.author | Xiao, Sheng | en_US |
dc.contributor.author | Kishi, Yasuhiro | en_US |
dc.contributor.author | Regev, Aviv | en_US |
dc.contributor.author | Kuchroo, Vijay | en_US |
dc.date.accessioned | 2014-03-10T20:33:53Z | |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | Wu, Chuan, Nir Yosef, Theresa Thalhamer, Chen Zhu, Sheng Xiao, Yasuhiro Kishi, Aviv Regev, and Vijay Kuchroo. 2013. “Induction of pathogenic Th17 cells by inducible salt sensing kinase SGK1.” Nature 496 (7446): 513-517. doi:10.1038/nature11984. http://dx.doi.org/10.1038/nature11984. | en |
dc.identifier.issn | 0028-0836 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878891 | |
dc.description.abstract | Th17 cells are highly proinflammatory cells critical for clearing extracellular pathogens and for induction of multiple autoimmune diseases1. IL-23 plays a critical role in stabilizing and reinforcing the Th17 phenotype by increasing expression of IL-23 receptor (IL-23R) and endowing Th17 cells with pathogenic effector functions2, 3. However, the precise molecular mechanism by which IL-23 sustains the Th17 response and induces pathogenic effector functions has not been elucidated. Here, we used transcriptional profiling of developing Th17 cells to construct a model of their signaling network and nominate major nodes that regulate Th17 development. We identified serum glucocorticoid kinase-1 (SGK1), a serine-threonine kinase4, as an essential node downstream of IL-23 signaling. SGK1 is critical for regulating IL-23R expression and stabilizing the Th17 cell phenotype by deactivation of Foxo1, a direct repressor of IL-23R expression. SGK1 has been shown to govern Na+ transport and salt (NaCl) homeostasis in other cells5, 6, 7, 8. We here show that a modest increase in salt concentration induces SGK1 expression, promotes IL-23R expression and enhances Th17 cell differentiation in vitro and in vivo, accelerating the development of autoimmunity. Loss of SGK1 abrogated Na+-mediated Th17 differentiation in an IL-23-dependent manner. These data demonstrate that SGK1 plays a critical role in the induction of pathogenic Th17 cells and provides a molecular insight into a mechanism by which an environmental factor such as a high salt diet triggers Th17 development and promotes tissue inflammation. | en |
dc.language.iso | en_US | en |
dc.relation.isversionof | doi:10.1038/nature11984 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637879/pdf/ | en |
dash.license | LAA | en_US |
dc.title | Induction of pathogenic Th17 cells by inducible salt sensing kinase SGK1 | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Nature | en |
dash.depositing.author | Wu, Chuan | en_US |
dc.date.available | 2014-03-10T20:33:53Z | |
dc.identifier.doi | 10.1038/nature11984 | * |
dash.contributor.affiliated | Thalhamer, Theresa | |
dash.contributor.affiliated | Zhu, Chen | |
dash.contributor.affiliated | Wu, Chuan | |
dash.contributor.affiliated | Yosef, Nir | |
dash.contributor.affiliated | Kuchroo, Vijay | |