Induction of pathogenic T(H)17 cells by inducible salt-sensing kinase SGK1

Chuan Wu, Nir Yosef, Theresa Thalhamer, Chen Zhu, Sheng Xiao, Yasuhiro Kishi, Aviv Regev, Vijay K. Kuchroo

Research output: Contribution to journalArticlepeer-review


T(H)17 cells (interleukin-17 (IL-17)-producing helper T cells) are highly proinflammatory cells that are critical for clearing extracellular pathogens and for inducing multiple autoimmune diseases(1). IL-23 has a critical role in stabilizing and reinforcing the T(H)17 phenotype by increasing expression of IL-23 receptor (IL-23R) and endowing T(H)17 cells with pathogenic effector functions(2,3). However, the precise molecular mechanism by which IL-23 sustains the T(H)17 response and induces pathogenic effector functions has not been elucidated. Here we used transcriptional profiling of developing T(H)17 cells to construct a model of their signalling network and nominate major nodes that regulate T(H)17 development. We identified serum glucocorticoid kinase 1 (SGK1), a serine/threonine kinase(4), as an essential node downstream of IL-23 signalling. SGK1 is critical for regulating IL-23R expression and stabilizing the T(H)17 cell phenotype by deactivation of mouse Foxo1, a direct repressor of IL-23R expression. SGK1 has been shown to govern Na+ transport and salt (NaCl) homeostasis in other cells(5-8). We show here that a modest increase in salt concentration induces SGK1 expression, promotes IL-23R expression and enhances T(H)17 cell differentiation in vitro and in vivo, accelerating the development of autoimmunity. Loss of SGK1 abrogated Na+-mediated T(H)17 differentiation in an IL-23-dependent manner. These data demonstrate that SGK1 has a critical role in the induction of pathogenic T(H)17 cells and provide a molecular insight into a mechanism by which an environmental factor such as a high salt diet triggers T(H)17 development and promotes tissue inflammation.
Original languageEnglish
Pages (from-to)513-517
Number of pages5
JournalNature (London)
Issue number7446
Early online date6 Mar 2013
StatePublished - 25 Apr 2013
Externally publishedYes


Dive into the research topics of 'Induction of pathogenic T(H)17 cells by inducible salt-sensing kinase SGK1'. Together they form a unique fingerprint.

Cite this