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DOI | 10.1038/s41467-018-05883-1 |
A non-conserved amino acid variant regulates differential signalling between human and mouse CD28 | |
Porciello, Nicla1; Grazioli, Paola2; Campese, Antonio F.3; Kunkl, Martina1; Caristi, Silvana1; Mastrogiovanni, Marta1; Muscolini, Michela4; Spadaro, Francesca5; Favre, Cedric6,7; Nunes, Jacques A.6; Borroto, Aldo8; Alarcon, Balbino8; Screpanti, Isabella3; Tuosto, Loretta1 | |
2018-03-14 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Italy; France; Spain |
英文摘要 | CD28 superagonistic antibodies (CD28SAb) can preferentially activate and expand immunosuppressive regulatory T cells (Treg) in mice. However, pre-clinical trials assessing CD28SAbs for the therapy of autoimmune diseases reveal severe systemic inflammatory response syndrome in humans, thereby implying the existence of distinct signalling abilities between human and mouse CD28. Here, we show that a single amino acid variant within the C-terminal proline-rich motif of human and mouse CD28 (P-212 in human vs. A(210) in mouse) regulates CD28-induced NF-kappa B activation and pro-inflammatory cytokine gene expression. Moreover, this Y(209)APP(212) sequence in humans is crucial for the association of CD28 with the Nck adaptor protein for actin cytoskeleton reorganisation events necessary for CD28 autonomous signalling. This study thus unveils different outcomes between human and mouse CD28 signalling to underscore the importance of species difference when transferring results from preclinical models to the bedside. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000427377800007 |
WOS关键词 | PHOSPHATIDYLINOSITOL 4-PHOSPHATE 5-KINASE ; MONOCLONAL-ANTIBODY TGN1412 ; CELL COSTIMULATORY RECEPTOR ; T-CELLS ; IMMUNOLOGICAL SYNAPSE ; ANTIGEN RECEPTOR ; IN-VITRO ; ACTIVATION ; RECRUITMENT ; SUPERAGONIST |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203967 |
专题 | 资源环境科学 |
作者单位 | 1.Sapienza Univ, Fdn Cenci Bolognetti, Ist Pasteur Italia, Dept Biol & Biotechnol Charles Darwin,Lab Affilia, I-00185 Rome, Italy; 2.Sapienza Univ, Dept Expt Med, I-00161 Rome, Italy; 3.Sapienza Univ, Fdn Cenci Bolognetti, Ist Pasteur, Dept Mol Med,Lab Affiliated, I-00161 Rome, Italy; 4.Fdn Cenci Bolognetti, Ist Pasteur, I-00161 Rome, Italy; 5.Ist Super Sanita, Confocal Microscopy Unit, NMR & Confocal Microscopy Area Core Facil, I-00161 Rome, Italy; 6.Aix Marseille Univ, Inst Paoli Calmettes, Ctr Rech Cancerol Marseille, Inserm U1068,CNRS UMR7258,Immun & Canc Team,UM105, F-13284 Marseille, France; 7.Immunotech SAS, Beckman Coulter, Life Sci Global Assay & Applicat Dev, F-13276 Marseille, France; 8.Autonomous Univ Madrid CSIC UAM, Spanish Natl Res Council, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain |
推荐引用方式 GB/T 7714 | Porciello, Nicla,Grazioli, Paola,Campese, Antonio F.,et al. A non-conserved amino acid variant regulates differential signalling between human and mouse CD28[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Porciello, Nicla.,Grazioli, Paola.,Campese, Antonio F..,Kunkl, Martina.,Caristi, Silvana.,...&Tuosto, Loretta.(2018).A non-conserved amino acid variant regulates differential signalling between human and mouse CD28.NATURE COMMUNICATIONS,9. |
MLA | Porciello, Nicla,et al."A non-conserved amino acid variant regulates differential signalling between human and mouse CD28".NATURE COMMUNICATIONS 9(2018). |
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