Nur77-mediated TRAF6 signalling protects against LPS-induced sepsis in mice

BACKGROUND: Nur77, a key member of the NR4A receptor subfamily, is involved in the regulation of inflammation and immunity. However, the in vivo regulatory roles of Nur77 in sepsis and the mechanisms involved remains largely elusive. In this study, we used Nur77-deficient (Nur77(−/−)) mice and investigated the function of Nur77 in sepsis. FINDINGS: Compared to wild-type (Nur77(+/+)) mice, Nur77(−/−) mice are more susceptible to LPS-induced sepsis and acute liver inflammation. Mechanistically, we observed that Nur77 can interact with TRAF6, a crucial adaptor molecule in the Toll-like receptor-interleukin 1 receptor (TLR-IL-1R) signalling pathway, in in vivo mouse model of sepsis. The interaction may affect TRAF6 auto-ubiquitination, thereby inhibiting NF-κB activation and pro-inflammatory cytokines production. CONCLUSIONS: These in vivo observations reveals an important protective role for Nur77 in LPS-induced sepsis through its regulation to TRAF6 signalling, and highlights the potential clinical application of Nur77 as a molecular target in prevention and/or treatment of sepsis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12950-016-0112-9) contains supplementary material, which is available to authorized users.