by the Milieu Intérieur Consortium (updated on 2018-03-06)


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Introduction

The enumeration and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative impact that environmental and genetic factors have on driving variation of innate and adaptive immune cell parameters in homeostatic conditions, we combined standardized flow cytometric analysis of blood leukocytes and genome-wide DNA genotyping in 1,000 healthy, unrelated individuals of western European ancestry. We show that smoking, together with age, sex and latent cytomegalovirus infection, are the main non-genetic factors affecting human variation in immune cell parameters, particularly those of adaptive cells. Genome-wide association studies identified 15 loci that control immunophenotypes, 13 of which were found in innate cells. Together, these results demonstrate that host genetic variation explains an important fraction of inter-individual differences in innate cell parameters, in contrast with adaptive cell parameters, which are primarily driven by life-long environmental exposures.

This user-friendly web interface provides vizualization tools to explore the effects of non-genetic and genetic factors controllling homeostasis of circulating white blood cells in healthy individuals from the Milieu Intérieur cohort. Implementation of these key determinants may improve diagnostic criteria and further the utility of cell phenotype laboratory measurements in the ultimate development of personalized strategies for patient management in the clinical setting.



Related publications

  • “The Milieu Intérieur study — An integrative approach for study of human immunological variance”, Thomas et al, Clinical Immunology, Volume 157, Issue 2, Pages 277-293. link
  • “Semi-automated and standardized cytometric procedures for multi-panel and multi-parametric whole blood immunophenotyping”. Hasan et al, Clinical Immunology, Volume 157, Issue 2, April 2015, Pages 261-276. link
  • “Automated flow cytometric analysis across large numbers of samples and cell types”. Chen et al, Clinical Immunology, Volume 157, Issue 2, April 2015, Pages 249-260. link
  • “Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges”. Piasecka et al, PNAS, Dec 2017. link

Gating Strategies for each of the 10 panels