High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation.

Autor: Abeler-Dörner L; Department of Immunobiology, King's College London, London, UK., Laing AG; Department of Immunobiology, King's College London, London, UK.; The Francis Crick Institute, London, UK., Lorenc A; Department of Immunobiology, King's College London, London, UK.; The Francis Crick Institute, London, UK., Ushakov DS; Department of Immunobiology, King's College London, London, UK.; The Francis Crick Institute, London, UK., Clare S; Wellcome Sanger Institute, Hinxton, UK., Speak AO; Wellcome Sanger Institute, Hinxton, UK., Duque-Correa MA; Wellcome Sanger Institute, Hinxton, UK., White JK; Wellcome Sanger Institute, Hinxton, UK., Ramirez-Solis R; Wellcome Sanger Institute, Hinxton, UK., Saran N; Department of Immunobiology, King's College London, London, UK., Bull KR; MRC Human Immunology Unit, University of Oxford, Oxford, UK., Morón B; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Iwasaki J; National Heart and Lung Institute, Imperial College London, London, UK., Barton PR; Cambridge Institute of Medical Research, University of Cambridge, Cambridge, UK., Caetano S; Department of Immunobiology, King's College London, London, UK.; Wellcome Sanger Institute, Hinxton, UK., Hng KI; Department of Immunobiology, King's College London, London, UK., Cambridge E; Wellcome Sanger Institute, Hinxton, UK., Forman S; Lydia Becker Institute of Immunology and Inflammation, Wellcome Trust Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Crockford TL; MRC Human Immunology Unit, University of Oxford, Oxford, UK., Griffiths M; Wellcome Sanger Institute, Hinxton, UK., Kane L; Wellcome Sanger Institute, Hinxton, UK., Harcourt K; Wellcome Sanger Institute, Hinxton, UK., Brandt C; Wellcome Sanger Institute, Hinxton, UK., Notley G; Wellcome Sanger Institute, Hinxton, UK., Babalola KO; European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK., Warren J; European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK., Mason JC; European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK., Meeniga A; European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK., Karp NA; Data Sciences & Quantitative Biology, Discovery Sciences, R&D Biopharmaceuticals, AstraZeneca, Cambridge, UK., Melvin D; Wellcome Sanger Institute, Hinxton, UK., Cawthorne E; MRC Human Immunology Unit, University of Oxford, Oxford, UK., Weinrick B; Department of Microbiology and Immunology, Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Rahim A; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada., Drissler S; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada., Meskas J; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada., Yue A; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada., Lux M; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada., Song-Zhao GX; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., Chan A; Department of Immunobiology, King's College London, London, UK., Ballesteros Reviriego C; Wellcome Sanger Institute, Hinxton, UK., Abeler J; Department of Economics, University of Oxford, Oxford, UK., Wilson H; Wellcome Sanger Institute, Hinxton, UK., Przemska-Kosicka A; Department of Immunobiology, King's College London, London, UK., Edmans M; MRC Human Immunology Unit, University of Oxford, Oxford, UK., Strevens N; Wellcome Sanger Institute, Hinxton, UK., Pasztorek M; Department of Immunobiology, King's College London, London, UK.; Department of Biomedical Science, University of Applied Sciences FH Campus Wien, Vienna, Austria., Meehan TF; European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK., Powrie F; The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK., Brinkman R; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.; Department of Bioinformatics, University of British Columbia, Vancouver, BC, Canada., Dougan G; Wellcome Sanger Institute, Hinxton, UK., Jacobs W Jr; Department of Microbiology and Immunology, Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY, USA., Lloyd CM; National Heart and Lung Institute, Imperial College London, London, UK., Cornall RJ; MRC Human Immunology Unit, University of Oxford, Oxford, UK., Maloy KJ; Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, UK., Grencis RK; Lydia Becker Institute of Immunology and Inflammation, Wellcome Trust Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Griffiths GM; Cambridge Institute of Medical Research, University of Cambridge, Cambridge, UK., Adams DJ; Wellcome Sanger Institute, Hinxton, UK., Hayday AC; Department of Immunobiology, King's College London, London, UK. adrian.hayday@kcl.ac.uk.; The Francis Crick Institute, London, UK. adrian.hayday@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2020 Jan; Vol. 21 (1), pp. 86-100. Date of Electronic Publication: 2019 Dec 16.
DOI: 10.1038/s41590-019-0549-0
Abstrakt: By developing a high-density murine immunophenotyping platform compatible with high-throughput genetic screening, we have established profound contributions of genetics and structure to immune variation (http://www.immunophenotype.org). Specifically, high-throughput phenotyping of 530 unique mouse gene knockouts identified 140 monogenic 'hits', of which most had no previous immunologic association. Furthermore, hits were collectively enriched in genes for which humans show poor tolerance to loss of function. The immunophenotyping platform also exposed dense correlation networks linking immune parameters with each other and with specific physiologic traits. Such linkages limit freedom of movement for individual immune parameters, thereby imposing genetically regulated 'immunologic structures', the integrity of which was associated with immunocompetence. Hence, we provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.
Databáze: MEDLINE