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

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

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
Volume11
Issue number3
DOIs
Publication statusPublished - 16 Mar 2016
Externally publishedYes

Keywords

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

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