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

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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]
Número total de Autores: 16
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 9
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 11, n. 3 MAR 16 2016.
Citações Web of Science: 0

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)

Processo FAPESP: 15/11868-7 - Triptases de mastócitos e a doença renal crônica experimental
Beneficiário:Lislaine Andrade Wensing
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado