Details

Autor(en) / Beteiligte

• 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
• Wong, G. William

Titel

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

Ist Teil von

• PloS one, 2016-03, Vol.11 (3), p.e0151638-e0151638

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.