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

Etienne Patin (1, 2) , Milena Hasan (3) , Jacob Bergstedt (4) , Vincent Rouilly (3, 2) , Valentina Libri (3) , Alejandra Urrutia (5, 3) , Cécile Alanio (5) , Petar Scepanovic (6, 7) , Christian Hammer (6, 7) , Friederike Jönsson (8) , Benoit Beitz (3) , Hélène Quach (1) , Yoong Wearn Lim (9) , Julie Hunkapiller (9) , Magge Zepeda (9) , Cherie Green (9) , Barbara Piasecka (3, 1) , Claire Leloup (9) , Lars Rogge (10, 3) , François Huetz (11) , Isabelle Peguillet (12) , Olivier Lantz (12) , Magnus Fontes (13, 4) , James Santo (14, 3) , Stéphanie Thomas (5, 3) , Jacques Fellay (9, 6) , Darragh Duffy (5, 3) , Lluis Quintana-Murci (1) , Matthew Albert (5, 9) , Consortium The Milieu Interieur

1 Génétique Evolutive Humaine - Human Evolutionary Genetics
2 C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative
3 CRT - Centre de Recherche Translationnelle - Center for Translational Science
4 Skane University Hospital [Lund]
5 Immunobiologie des Cellules dendritiques
6 EPFL - Ecole Polytechnique Fédérale de Lausanne
7 SIB - Swiss Institute of Bioinformatics [Lausanne]
8 Anticorps en Thérapie et Pathologie
9 Genentech, Inc. [San Francisco]
10 Immunorégulation
11 Biologie des Populations Lymphocytaires
12 Institut Curie [Paris]
13 IGDA - International Group for Data Analysis
14 Immunité Innée - Innate Immunity

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.

Domaines: Immunologie

Etienne Patin, Milena Hasan, Jacob Bergstedt, Vincent Rouilly, Valentina Libri, et al.. Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors. Nature Immunology, 2018, 19 (3), pp.302 - 314. ⟨10.1038/s41590-018-0049-7⟩. ⟨pasteur-01768943⟩