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

• Published in: PloS one Vol. 11; no. 3
• Main Authors: Zhou, Saijun, Tanaka, Kumiko, O'Keeffe, Meredith, Qi, Miao, El-Assaad, Fatima, Weaver, James C, Chen, Gang, Weatherall, Christopher, Wang, Ying, Giannakopoulos, Bill, Chen, Liming, Yu, DeMint, Hamilton, Matthew J, Wensing, Lislaine A, Stevens, Richard L, Krilis, Steven A
• Format: Journal Article
• Language: English
• Published: Public Library of Science 16-03-2016
• Subjects: Cellular signal transduction; Dendritic cells; Genetic aspects; Immune response regulation; Properties; Signaling peptides and proteins
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0151638

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.sup.+ 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.sup.+ 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.sup.+ DCs from WT mice induced natural killer (NK) cells to produce much more interferon-[gamma] (IFN-[gamma]) than comparable DCs from RasGRP4-null mice. The ability of LPS-responsive MCs to cause NK cells to increase their expression of IFN-[gamma] was also dependent on this intracellular signaling protein. The discovery that RasGRP4 is required for CD117.sup.+ 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.