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

Author(s):Show less -

Zhou, Saijun ^{[1, 2, 3, 4]} ; Tanaka, Kumiko ^{[1, 2]} ; O'Keeffe, Meredith ^[5] ; Qi, Miao ^{[1, 2]} ; El-Assaad, Fatima ^{[1, 2]} ; Weaver, James C. ^{[1, 2, 6]} ; Chen, Gang ^{[1, 2]} ; Weatherall, Christopher ^{[1, 2]} ; Wang, Ying ^{[1, 2]} ; Giannakopoulos, Bill ^{[1, 2]} ; Chen, Liming ^{[3, 4]} ; Yu, DeMint ^{[3, 4]} ; Hamilton, Matthew J. ^{[7, 8]} ; Wensing, Lislaine A. ^[9] ; Stevens, Richard L. ^{[1, 2, 7]} ; Krilis, Steven A. ^{[1, 2]}

Affiliation

^[1] Univ New S Wales, St George Hosp, Dept Infect Dis Immunol & Sexual Hlth, Sydney, NSW - Australia

^[2] Univ New S Wales, Fac Med, St George & Sutherland Clin Sch, Sydney, NSW - Australia

^[3] Tianjin Med Univ, Lab Hormones & Dev, Metab Hosp, Minist Hlth, Tianjin, TJ - Peoples R China

^[4] Tianjin Med Univ, Tianjin Inst Endocrinol, Tianjin, TJ - Peoples R China

^[5] Burnet Inst, Dendrit Cell Res Lab, Immun Vaccines & Immunisat, Prahran, Vic - Australia

^[6] St George Hosp, Dept Cardiol, Sydney, NSW - Australia

^[7] Univ Newcastle, Sch Biomed Sci & Pharm, Callaghan, NSW 2308 - Australia

^[8] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 - USA

^[9] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 11, n. 3 MAR 16 2016.
• Web of Science Citations: 0

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-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(+) 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. (AU)

• FAPESP's process: 15/11868-7 - Mast cell tryptases and experimental chronic kidney disease
• Grantee: Lislaine Andrade Wensing
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor