CD117+ dendritic and mast cells are dependent on RasGRP4 to function as accessory cells for optimal natural killer cell-mediated responses to lipopolysaccharide

Saijun Zhou, Kumiko Tanaka, Meredith O'Keeffe, Miao Qi, Fatima El-Assaad, James C Weaver, Gang Chen, Christopher Weatherall, Ying Wang, Bill M Giannakopoulos, Liming Chen, De Mint Yu, Matthew J. Hamilton, Lislaine A. Wensing, Richard L. Stevens, Steven A Krilis

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5 Citations (Scopus)


Ras guanine nucleotide-releasing protein-4 (RasGRP4) is an evolutionarily conserved calcium-regulated, guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor. While an important intracellular signaling protein for CD117+ mast cells (MCs), its roles in other immune cells is less clear. In this study, we identified a subset of in vivo-differentiated splenic CD117+ dendritic cells (DCs) in wild-type (WT) C57BL/6 mice that unexpectedly contained RasGRP4 mRNA and protein. In regard to the biologic significance of these data to innate immunity, LPS-treated splenic CD117+ DCs from WT mice induced natural killer (NK) cells to produce much more interferon-γ (IFN-γ) than comparable DCs from RasGRP4-null mice. The ability of LPS-responsive MCs to cause NK cells to increase their expression of IFN-γ was also dependent on this intracellular signaling protein. The discovery that RasGRP4 is required for CD117+ MCs and DCs to optimally induce acute NK cell-dependent immune responses to LPS helps explain why this signaling protein has been conserved in evolution.

Original languageEnglish
Article numbere0151638
Number of pages18
JournalPLoS ONE
Issue number3
Publication statusPublished - 16 Mar 2016
Externally publishedYes


  • NK cells
  • spleen
  • cytokines
  • blood
  • chemokines
  • expressed sequence tags
  • B cells
  • flow cytometry

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