Early-life Immune Imprinting and Inflammatory Diseases
Group Leader
Our team studies neonatal immunity. We are particularly interested in mapping the mucosal cell subsets carrying the inheritance of environmental exposure from early-life to adult with the ultimate objective of developing IBD and asthma therapeutic strategies.
We aim to go from a better understanding of early-life immune cell imprinting to new therapeutic strategies for chronic inflammatory disorders.
Inflammatory Bowel Disease (IBD) and asthma respectively represent poorly understood inflammatory disorders of the intestines and lungs. These diseases do not have a cure and commonly increased in prevalence in the last 40 years in western countries where they imposed substantial morbidity and economic burden on populations. During the period following birth, our body is newly exposed to food and microorganisms. Significant evidence indicates that such environmental exposure during early childhood can favor the development of immune-related disorders and allergic reactions in adults.
Specific immune cells, defined as “imprinted”, are educated by the environment exclusively during the early-life period with long-term consequences on disease susceptibility in experimental models of intestinal inflammation and allergies in animals. It appears critical to identify these “imprinted” immune cells in animals and humans as they may be paramount in IBD and asthma development.
However, few have been identified and properly characterized so far as methods to track down imprinting have not yet been developed.
Our research group establishes original screening strategies combined with cell biology and transcriptomic approaches to uncover and study immune cells imprinted by the neonatal environment. Our goal is to identify specific neonatal imprinting markers that could be targeted to develop predictive diagnostic and therapeutic strategies for IBD and asthma in adults.
Team members
Research Scientists
Thomas Gensollen (CNRS)
Pauline Schmitt (University)
Research Engineer
Manon Gimbert
Claire Guillen
Gensollen et al. Macrophages of embryonic origin function during early life to determine host iNKT cell levels at barrier surfaces. Nat Immunol
Gensollen, Blumberg. Correlation between early-life regulation of the immune system by microbiota and allergy development. J Allergy Clin Immunol
Gensollen et al. How colonization by microbiota in early life shapes the immune system. Science
Gensollen et al. Functional polymorphisms in the regulatory regions of the VNN1 gene are associated with susceptibility to inflammatory bowel diseases. Inflamm Bowel Dis
Our work is financially supported by the Fondation pour la Recherche Médicale (FRM) program “Amorçage Jeunes Equipes”.
The complete list of our publications is available through Pubmed
- Millet, V.*, Gensollen, T.*, Maltese, M.*, Serrero, M., Lesavre, S., Bourges C., Pitaval C., Cadra S., Chasson L., Vu Manh T.P., Masse M., Martinez-Garcia, J., Tranchida F., Shintu L., Mostert K., Strauss E., Lepage P., Chamaillard M., Broggi A., Peyrin-biroulet L., Grimaud J.L., Naquet P., Galland F. (2022) Harnessing the Vnn1 pantetheinase pathway boosts SCFA production and mucosal protection in colitis. Gut, doi:10.1136/gutjnl-2021-325792
- Gensollen, T., Lin, X., Zhang, T., Pyzik, M., See, P., Glickman, J.N., Ginhoux, F., Waldor, M., Salmi, M., Rantakari, P., Blumberg, R.S. (2021) Macrophages of embryonic origin function during early life to determine host iNKT cell levels at barrier surfaces. Nat Immunol, 22(6), 699–710
- Exley, M.A., Gensollen, T., Blumberg, R.S. (2021) A nano-engager for iNKT cells in cancer. Nat Cancer, 1 (11), 1032-1034
- Grootjans, J., Krupka, N., Hosomi, S., Matute, J.D., Hanley, T., Saveljeva, S., Gensollen, T., Heijmans, J., Li, H., Limenitakis, J.P., Ganal-Vonarburg, S.C., Suo, S., Luoma, A.M., Shimodaira, Y., Duan, J., Shih, D.Q., Conner, M.E., Glickman, J.N., Fuhler, G.M., Palm, N.W., de Zoete, M.R., van der Woude, C.J., Yuan, G.-C., Wucherpfennig, K.W., Targan, S.R., Rosenstiel, P., Flavell, R.A., McCoy, K.D., Macpherson, A.J., Kaser, A., Blumberg, R.S., Zoete, M.R. de, Woude, C.J. van der, Yuan, G.-C., Wucherpfennig, K.W., Targan, S.R., Rosenstiel, P., Flavell, R.A., McCoy, K.D., Macpherson, A.J., Kaser, A., Blumberg, R.S. (2019) Epithelial endoplasmic reticulum stress orchestrates a protective IgA response. Science, 363:993–8
- Iyer, S.S., Gensollen, T., Gandhi, A., Oh, S.F., Neves, J.F., Collin, F., Lavin, R., Serra, C., Glickman, J., de Silva, P.S.A., Sartor, R.B., Besra, G., Hauser, R., Maxwell, A., Llebaria, A., Blumberg, R.S. (2018) Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses. Cell, 173:1123–1134.e11
- Giessner, C., Millet, V., Mostert, K.J., Gensollen, T., Vu Manh, T.-P., Garibal, M., Dieme, B., Attaf-Bouabdallah, N., Chasson, L., Brouilly, N., Laprie, C., Lesluyes, T., Blay, J.Y., Shintu, L., Martin, J.C., Strauss, E., Galland, F., Naquet, P. (2018) Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity. Life Sci Alliance, 1:e201800073
- Zeissig, S., Peuker, K., Iyer, S., Gensollen, T., Dougan, S.K., Olszak, T., Kaser, A., Blumberg, R.S. (2017) CD1d-Restricted pathways in hepatocytes control local natural killer T cell homeostasis and hepatic inflammation. Proc Natl Acad Sci USA, 114:10449–54
- Gensollen, T., Blumberg, R.S. (2017) Correlation between early-life regulation of the immune system by microbiota and allergy development. J Allergy Clin Immunol, 139:1084–91
- Gensollen, T., Iyer, S.S., Kasper, D.L., Blumberg, R.S. (2016) How colonization by microbiota in early life shapes the immune system. Science, 352:539–44
- Rommelaere, S., Millet, V., Vu Manh, T.-P., Gensollen, T., Andreoletti, P., Cherkaoui-Malki, M., Bourges, C., Escalière, B., Du, X., Xia, Y., Imbert, J., Beutler, B., Kanai, Y., Malissen, B., Malissen, M., Tailleux, A., Staels, B., Galland, F., Naquet, P. (2014) Sox17 regulates liver lipid metabolism and adaptation to fasting. PLoS One, 9:e104925
- Rommelaere, S., Millet, V., Gensollen, T., Bourges, C., Eeckhoute, J., Hennuyer, N., Baugé, E., Chasson, L., Cacciatore, I., Staels, B., Pitari, G., Galland, F., Naquet, P. (2013) PPARalpha regulates the production of serum Vanin-1 by liver. FEBS Lett, 587:3742–8
- Gensollen, T., Bourges, C., Rihet, P., Rostan, A., Millet, V., Noguchi, T., Bourdon, V., Sobol, H., Dubuquoy, L., Bertin, B., Fumery, M., Desreumaux, P., Colombel, J.-F., Chamaillard, M., Hebuterne, X., Hofman, P., Naquet, P., Galland, F. (2013) Functional polymorphisms in the regulatory regions of the VNN1 gene are associated with susceptibility to inflammatory bowel diseases. Inflamm Bowel Dis, 19:2315–25.