About

The Milieu Intérieur project provides insight into the core of human diversity by dissecting the interplay between genetics and environment and their impact on the immune system. https://www.youtube.com/watch?v=IXlKElDJMc8

The Milieu Intérieur Project

While the immune system is highly complex and responses are known to vary across individuals and populations, medical practices and public health policies remain based on a single model of patient care and drug development. The Milieu Intérieur project was initiated specifically to address this discrepancy. The primary objective of our work is to establish the boundaries of a “healthy” immune response and define the determinants of immune response variation, integrating the relationship among genetics, epigenetics and the environment. The specific aims of the Milieu Intérieur project are to: (i) define the naturally-occurring variability of human immune response, (ii) assess how this variation is genetically, epigenetically or environmentally controlled, (iii) understand how this genetic/phenotypic variation may account for differences in susceptibility to infection, therapeutic treatment or vaccine response, and (iv) ascertain the variation and role of the microbiota in regulating immune programs. MI Design

The Milieu Intérieur dataset. Click to enlarge.

Milieu Intérieur 2 (MI2) – The next phase

For the next 5-year period, we will build on the existing solid foundations to extend our understanding of how genetics, microbiome and environmental factors determine immune response variability. For this we will

  • Explore the genetic, microbiome and environmental determinants of immune response variation in the adult population
  • Define the drivers of immune response variation in extreme ages and other geographic regions
  • Apply a systems immunology approaches to human disease to ensure that relevant clinical discoveries will be translated into improved patient care

The Milieu Intérieur project is supported by the French National Ministry of Research. This program is part of a larger French government’s Invest in the Future economic stimulus plan called Investissement d’Avenir  – Laboratoire d’Excellence (LabEx).

Teams

Collaborations

Title – Role of HLA ClassII in the humoral response
Person in charge – John Altin
Affiliation – Altin Laboratory, TGEN

Title – Role of HLA ClassII in the humoral response
Person in charge – John Altin
Affiliation – Altin Laboratory, TGEN

Title – Analysis of cellular signaling pathways and genetic networks in chronic inflammatory diseases patient samples
Person in charge – Lars Rogge
Affiliation – Institut Pasteur

Title – Characterising the relationship between polygenic risk for autoimmunity and immune responses
Person in charge – Zia Khan (Genentech)
Affiliation – Genentech Inc.

Title – Understanding the effects of CMV infection
Person in charge – Amir Horowitz
Affiliation – Horowitz Laboratory /Icahn School of Medicine at Mount Sinai

Title – Immune function in patient undergoing immune modulating interventions
Person in charge – Susanne Dam Poulson
Affiliation – Department of Infectious Disease, University of Copenhagen

Title – Inter-individual variability of the oxylipin response
Persons in charge – Cecile Gladine and Andre Mazur
Affiliation – UMR 1019 INRA/Université Clermont Auvergne

Title – Determining the frequency of CD3+CD8+CD16+ T cells in the healthy population
Person in charge – Nicolas Degauque
Affiliation – Centre Hospitalier, Universitaire de Nantes

Title – Epigenomic variation in immune cells associated with aging
Person in charge – Duygu Ucar
Affiliation – Jackson Laboratory for Genomic Medicine

Title – Causes of natural variation in the immune system – a mendelian Randomisation
Person in charge – George Davey-Smith
Affiliation – Medical Research Council Integrative Epidemiology Unit (MRC IEU), University of Bristol

Title – Variability in induced immune responses to TLR stimulation
Person in charge – Allyson Byrd
Affiliation – Genentech Inc.

Title – Late-Spike haplotype dosage association with immune cell type abundances or marker abundances
Person in charge – Soumya Raychaudhuri
Affiliation – Broad Insitute of Harvard and MIT.

Title – Comparison of the Polygenic score between individuals with Bipolar disorder and the healthy population
Person in charge – Stephane Jamain
Affiliation – INSERM U955

Title – Comparison of Milieu Intérieur immune response data with samples from patients with primary immunodeficiencies
Person in charge – Petter Brodin
Affiliation – Karolinska Institutet

Title – Validity of a new analysis method on published flow cytometry data
Person in charge – Wolfgang Losert
Affiliation – University of Maryland

Title – Soluble immune inhibitory factors as drivers of immune (dys)function in health and disease
Person in charge – Sisse Rye Ostrowski
Affiliation – Department of Clinical Immunology, University of Copenhagen

Title – Identification of the dietary patterns to explain gut microbiome configurations
Person in charge – Julien Tap
Affiliation – Danone Research

Title – Role of inborn errors of immunity in response to SAR-CoV2 infection
Person in charge – Jean-Laurent Casanova
Affiliation – INSERM

Title – Integrating genetic and microbiome risk profiles for disease prediction using multivariate analysis
Person in charge – Petar Scepanovic
Affiliation – Roche Basel, Switzerland
Project with pRED, Roche aims to test the hypothesis that the host genetics and microbiome act in an independent manner. Through the use of polygenic risk scores and microbiome dysbiosis index, we aim to derive prediction models for various diseases that could be of relevance for healthy individuals.

Title – Establishing a baseline gut microbiota index of healthy vounteers
Person in charge – Rafi Ahmad
Affiliation – Inland Norway University
Baseline Gut Microbiota Index” project aims to facilitate the understanding of immune responses in relation to physiology, genetics, and environment from a microbiome perspective. This would enable a better understanding of variables regulating and/or influencing the immune system, which aids in understanding the role of microbiota in immune responses along with identifying therapeutic targets enabling personalised treatment

Title – MICMAT
Person in charge – Christophe Boetto, Hugues Aschard
Affiliation – Institut Pasteur
Baseline Gut Microbiota Index” project aims to facilitate the understanding of immune responses in relation to physiology, genetics, and environment from a microbiome perspective. This would enable a better understanding of variables regulating and/or influencing the immune system, which aids in understanding the role of microbiota in immune responses along with identifying therapeutic targets enabling personalised treatment.

Title – Exploring Pathogenic Mechanisms of Chronic Inflammatory Diseases : unresolved issues in IL-23/IL-17 biology
Person in charge – Ikram Mezgiche, Elisabetta Bianchi, Lars Rogge
Affiliation – Institut Pasteur
Our project aims to improve our understanding of the so-called “IL-23/IL-17 axis” in the pathophysiology of axial spondyloarthritis, psoriatic arthritis, and psoriasis. We will address the effects of IL-23 on distinct cell populations from patients and how is expression of the IL-23 receptor regulated.

Data visualization

Visualize the data from our Immunity paper “Functional analysis via standardized whole-blood stimulation systems defines the boundaries of a healthy immune response to complex stimuli” Duffy et al Slide4

Partners

Featured Projects

Featured Publications