sNASP inhibits TLR signaling to regulate immune response in sepsis

Feng Ming Yang, Yong Zuo, Wei Zhou, Chuan Xia, Bumsuk Hahm, Mark Sullivan, Jinke Cheng, Hui Ming Chang, Edward T.H. Yeh

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21 引文 斯高帕斯(Scopus)


Many Toll-like receptors (TLRs) signal through TNF receptor-associated factor 6 (TRAF6) to activate innate immune responses. Here, we show that somatic nuclear autoantigenic sperm protein (sNASP) binds to TRAF6 to prevent TRAF6 autoubiquitination in unstimulated macrophages. Following LPS stimulation, a complex consisting of sNASP, TRAF6, IRAK4, and casein kinase 2 (CK2) is formed. CK2 phosphorylates sNASP at serine 158, allowing sNASP to dissociate from TRAF6. Free TRAF6 is then autoubiquitinated, followed by activation of downstream signaling pathways. In sNasp S158A knockin (S158A-KI) mice, LPS-treated macrophages could not phosphorylate sNASP, which remained bound to TRAF6. S158A-KI mice were more susceptible to sepsis due to a marked reduction in IL-1ß, TNF-a, and IFN-? production accompanied by an inability to clear bacteria and recruit leukocytes. Furthermore, phosphorylation-regulated release of sNASP from TRAF6 is observed following activation of TLR-1, -2, -4, -5, and -6. Thus, sNASP is a negative regulator of TLR signaling to modulate the innate immune response.
頁(從 - 到)2459-2472
期刊Journal of Clinical Investigation
出版狀態已發佈 - 6月 1 2018

ASJC Scopus subject areas

  • 一般醫學


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