Skip to main content

Dr. Thomas Gensollen - From a better understanding of mucosal early-life immune cells imprinting to therapeutics

 

Thomas Gensollen

Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

From a better understanding of mucosal early-life immune cells imprinting to therapeutics

During the period following birth, the mucosal tissues are newly exposed to a large spectrum of antigens from diet and commensal bacteria. Significant evidence indicates that such environmental exposure during early childhood can favor the development of immune-related disorders and allergic reactions in adults, as observed in Inflammatory bowel diseases (IBD) or asthma. IBD and asthma are respectively chronic inflammatory disorders of the intestines and airways arising from not fully understood heterogenic environment, genetic and immune system interactions. Therefore, it is critical to identify the immune cells regulated by environmental cues during the neonatal period of life and how they affect the development of diseases in later life in mucosal tissues. Recent studies identified few subsets of mucosal immune cells regulated in such manners. Among them, invariant natural killer T cells (iNKT) are representing a rare subset of T cells with innate-like properties whose levels are suppressed by microbiota in early, but not later, life in mice. Therefore, if the proper microbial signal is not provided during a restricted period of neonatal life, colonic and lung iNKT cell levels are increased in the adult animal, leading to increased susceptibility to experimental models of colitis and asthma. Motivated to understand the mechanisms by which the microbiota can regulate immune T cells in an age-restricted and long-lasting manner, we provided evidence for the first time that embryonic-derived macrophages support an extrathymic pathway of immune development within mucosal tissues specifically during early life, which determines the ability of these organs to receive iNKT cells and allow them to establish local residency. It suggested iNKT cells may be representative of a broader family of cells, which residency is regulated by neonatal developmental processes and environmental exposure: the early-life derived resident cells family.

Selected publications

  • Gensollen T, Lin X, Zhang T, Pyzik M, See P, Glickman JN et al. Macrophages of embryonic origin function during early life to determine host iNKT cell levels at barrier surfaces. Nature Immunology 2021;22(6), 699–710
  • Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science 2016;352:539–44
  • Gensollen T, Blumberg RS. Correlation between early-life regulation of the immune system by microbiota and allergy development. J Allergy Clin Immunol 2017;139:1084–91

Contact: Olivier Neyrolles (Olivier.Neyrolles@ipbs.fr)

27 Sep

17:00 - 18:00

Online seminar