Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors

Etienne Patin, Milena Hasan, Jacob Bergstedt, Vincent Rouilly, Valentina Libri, Alejandra Urrutia, Cécile Alanio, Petar Scepanovic, Christian Hammer, Friederike Jönsson, Benoît Beitz, Helene Quach, Yoong Wearn Lim, Julie Hunkapiller, Magge Zepeda, Cherie Green, Barbara Piasecka, Claire Leloup, Lars Rogge, François HuetzIsabelle Peguillet, Olivier Lantz, Magnus Fontes, James P. Santo, Stéphanie Thomas, Jacques Fellay, Darragh Duffy, Lluis Quintana-Murci, Matthew L Albert, Milieu Intérieur Consortium

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.
Originalspråkengelska
Sidor (från-till)302–314
TidskriftNature Immunology
Volym19
DOI
StatusPublished - 2018 feb. 23

Ämnesklassifikation (UKÄ)

  • Immunologi inom det medicinska området

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