2. Academic Validation
  3. CD117+ Dendritic and Mast Cells Are Dependent on RasGRP4 to Function as Accessory Cells for Optimal Natural Killer Cell-Mediated Responses to Lipopolysaccharide

CD117+ Dendritic and Mast Cells Are Dependent on RasGRP4 to Function as Accessory Cells for Optimal Natural Killer Cell-Mediated Responses to Lipopolysaccharide

  • PLoS One. 2016 Mar 16;11(3):e0151638. doi: 10.1371/journal.pone.0151638.
Saijun Zhou 1 2,  Kumiko Tanaka 1,  Meredith O'Keeffe 3,  Miao Qi 1,  Fatima El-Assaad 1,  James C Weaver 1 4,  Gang Chen 1,  Christopher Weatherall 1,  Ying Wang 1,  Bill Giannakopoulos 1,  Liming Chen 2,  DeMint Yu 2,  Matthew J Hamilton 5 6,  Lislaine A Wensing 7,  Richard L Stevens 1 5,  Steven A Krilis 1
Affiliations

Affiliations

  • 1 Department of Infectious Diseases, Immunology, and Sexual Health, St. George Hospital, and the St. George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
  • 2 Laboratory of Hormones and Development (Ministry of Health), Metabolic Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, TJ, China.
  • 3 Dendritic Cell Research Laboratory, Immunity Vaccines and Immunisation, Burnet Institute, Prahran, Melbourne, Victoria, Australia.
  • 4 Department of Cardiology, St. George Hospital, Sydney, New South Wales, Australia.
  • 5 School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
  • 6 Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, United States of America.
  • 7 Departament of Immunology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.
PMID: 26982501 DOI: 10.1371/journal.pone.0151638
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.

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