High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation.
Animals
Citrobacter
/ immunology
Enterobacteriaceae Infections
/ immunology
Female
Genetic Variation
/ genetics
High-Throughput Screening Assays
/ methods
Humans
Immunophenotyping
/ methods
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Salmonella
/ immunology
Salmonella Infections
/ immunology
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
27
03
2019
accepted:
29
10
2019
pubmed:
18
12
2019
medline:
16
4
2020
entrez:
18
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31844327
doi: 10.1038/s41590-019-0549-0
pii: 10.1038/s41590-019-0549-0
pmc: PMC7338221
mid: EMS86707
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
86-100Subventions
Organisme : Cancer Research UK
ID : FC001093
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R007748/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 102972
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107059
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC001093
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM118417
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006370
Pays : United States
Organisme : Medical Research Council
ID : FC001093
Pays : United Kingdom
Organisme : Wellcome Trust (Wellcome)
ID : 100156/Z/12/Z
Pays : International
Organisme : Medical Research Council
ID : MC_UU_00008/6
Pays : United Kingdom
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