- Title
- CD117⁺ dendritic and mast cells are dependent on RasGRP4 to function as accessory cells for optimal natural killer cell-mediated responses to lipopolysaccharide
- Creator
- Zhou, Saijun; Tanaka, Kumiko; Chen, Liming; Yu, DeMint; Hamilton, Matthew J.; Wensing, Lislaine A.; Stevens, Richard L.; Krilis, Steven A.; O'Keeffe, Meredith; Qi, Miao; El-Assaad, Fatima; Weaver, James C.; Chen, Gang; Weatherall, Christopher; Wang, Ying; Giannakopoulos, Bill
- Relation
- NHMRC.630402 http://purl.org/au-research/grants/nhmrc/630402
- Relation
- PLoS One Vol. 11, Issue 3, no. e0151638
- Publisher Link
- http://dx.doi.org/10.1371/journal.pone.0151638
- Publisher
- Public Library of Science (PLoS)
- Resource Type
- journal article
- Date
- 2016
- Description
- 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.
- Subject
- Ras guanine nucleotide-releasing protein-4 (RasGRP4); diacylglycerol/phorbol ester receptor; lipopolysaccharide
- Identifier
- http://hdl.handle.net/1959.13/1338520
- Identifier
- uon:28037
- Identifier
- ISSN:1932-6203
- Rights
- © 2016 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Language
- eng
- Full Text
- Reviewed
- Hits: 21799
- Visitors: 22630
- Downloads: 423
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 800 KB | Adobe Acrobat PDF | View Details Download |