Journal
NATURE IMMUNOLOGY
Volume 21, Issue 1, Pages 86-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41590-019-0549-0
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Funding
- Wellcome Trust [100156/Z/12/Z, 102972/Z/13/Z, Z10661/Z/18/Z, Z03128/Z/16/Z, FC001093]
- European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant [656347]
- National Institutes of Health (NIH) Common Fund [UM1 HG006370]
- Genome BC [SOF152, 252FLO]
- Natural Sciences and Engineering Research Council of Canada
- International Society for Advancement of Cytometry Genome Canada
- National Institute of General Medical Sciences [R01GM118417]
- Canadian Institutes of Health Research
- National Institute for Health Research
- NIH [AI026170]
- Wellcome Senior Fellowship in Basic Biomedical Science [107059/Z/15/Z]
- Francis Crick Institute - Cancer Research UK [FC001093]
- UK Medical Research Council [FC001093]
- MRC [MC_UU_00008/6] Funding Source: UKRI
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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.
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