Jean-François MOREAU

 Who am I ? ► link to a short CV

Professor of Medical Immunology (University of Bordeaux)
Pathologist – Immunology (Bordeaux University Hospital)

> My Research Project
Our project is based on the idea that mobility is at the center of immunity. The recently discovered diffuse tissue distribution of resident memory T cells (TRM), which don’t recirculate, calls into question analyses of immunity based on blood cells. These TRM account for most T cells residing in barrier epithelia and any organ. They sit in and travel through the extracellular matrix (ECM) between all the cells that constitute tissues and organs.

We hypothesize that as life appeared on Earth as unicellular, cells had to be mobile to explore their environment to survive. The transition toward organized group of cells (multicellular organisms) sets up mechanisms that control this mobility. As a result, individual cells ultimately lose mobility; cells in an organ are anchored to each other and immobile. Only one type of cell escaped this loss of mobility: these are cells of the immune system. Where are these mobile cells? They are mobile between the cells that constitute organ and tissues, in the ECM. The ECM plays many roles in maintaining the societies of cells and is instrumental to the unicellular to multicellular transition as it is shown in Volvox.

At the same time, an organism is made of a group of cells. To function together, they need to communicate. Three means of communication between cells can be distinguished. The quantity of information and the speed of communication is inversely proportional in these three systems. I give three examples where cell mobility is important to consider. First, primary tumors are made of immobile cells, but which can become again mobile, with accumulating mutations. They seed other locations and generate metastasis. Second, there is a group of immune deficiencies where cells of the immune system lose their full mobility due to a mutation of a gene responsible for the control of actin polymerisation. Third, aging of ECM in aging individuals changes the context of living cells and diminishes mobility of immune cells.

We propose an update of the theoretical framework of immunosenescence, based on a novel hypothesis: the increasing stiffness and cross-linking of the senescent ECM lead to progressive immunodeficiency due to an age-related decrease in T cell mobility and the death of these cells. A key element of this mechanism is the mechanical stress to which the cell cytoplasm and nucleus are subjected during passage through the ECM. This hypothesis is based on an “evo-devo” perspective bringing together some major characteristics of aging, to create a single interpretive framework for immunosenescence.

This work develops following two axes :
– one conceptual : transition from unicellular to multicellular life, origin of the immune system, cell mobility as a factor explaining life complexity, information flux between group of cells.
– one experimental :
–> mouse model of progeroid syndrome
–> in vivo examination of immune cell mobility in tissue by in vivo imaging
–> aging in collaboration with Prof Claudio Franceschi team at University of Bologna
–> stress of nucleus and consequences on epigenetics, transcriptomics and functions of T lymphocytes

> E-mail me here: jean-francois.moreau@u-bordeaux.fr