The François Jacob Institute of Biology brings together five departments and three services
The last two years in scientific news
Highlight | Scientific result | Immune system
Through an international collaboration, researchers from the LRTS laboratory (IRCM/CEA-Jacob) have characterized the cellular and molecular events regulating the balance between fibrotic repair and tissue regeneration and have identified a key player in this balance : macrophages. This study, published in Science Advances, opens up a new therapeutic perspective for the treatment of pathological tissue lesions.
The ability to repair tissue is
essential for the survival of an organism. It involves the restoration of
tissue architecture and tissue function after injury. Two processes can take
place in the injured tissue: regeneration (to maintain function) or healing.
Tissue regeneration occurs through
the proliferation of cells that retain the ability to divide, or replacement by
tissue stem cells.
Wound healing occurs through the
formation of connective (fibrous) tissue that provides architectural stability
so that the altered tissue is able to function.
For example, the skin, which acts
as a barrier essential to maintaining the body's integrity, is at the forefront
of the response to environmental aggression. The initial scar response consists
of the formation of tissue to compensate for the loss of substance and restore
its barrier function. However, when the inflammation persists, a pathological
scar response takes place, leading to the development of fibrous tissue: this
is the process of fibrosis1.
Skin lesions mostly result in
fibrotic scars, but may in some cases give rise to a beneficial regenerative
As part of an international
collaboration, researchers from the LRTS laboratory (IRCM) have characterized
the cellular and molecular events regulating the balance between fibrotic repair
and tissue regeneration and have identified a key player in this balance:
This study is based on the use of a
mouse model mimicking the repair process following a skin injury. The
researchers showed the importance of macrophages2 during the early stages of
tissue repair and that their persistence over time in the skin wound was
directly linked to a fibrotic process.
In addition, macrophages present
late in the skin wound phagocyte and degrade an inhibitor (SFRP4) of a major
metabolic pathway, the Wnt pathway. This leads to chronic activation of this
pathway and consequently to skin fibrosis. The suppression of phagocytosis is
sufficient to reverse the balance between fibrosis and skin regeneration. This
mechanism would thus be a new pathway to target for the repair of skin
fibrosis. In addition, this study showed that elements involved in the
reconstruction of the damaged environment (such as fibronectin) could be key
mediators in the mechanism of triggered phagocytosis.
This analysis has been deepened by
studying the phenomenon in patients suffering from a chronic, recurrent and
highly incapacitating skin pathology: suppurated hidradenitis. The lack of
curative treatment and the recurrent nature of hidradenitis complicate its
The researchers observed in these
patients that phagocytosis of the Wnt pathway inhibitor by macrophages was
perfectly correlated with wound repair by a fibrotic process.
These results indicate that the
mechanism identified is a major contributor to skin fibrosis and underline the
importance of modulation of the Wnt pathway in tissue repair. Modulation of the
regenerative activity of macrophages in this context opens up a new therapeutic
perspective in the treatment of pathological or injury-induced tissue damage.
Phagocytosis of Wnt inhibitor SFRP4 by late wound macrophages drives chronic Wnt activity for fibrotic skin healing I Science Advances
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.