innate lymphoid cells to the rescue ⋅ Inserm, From science to health

Cells that participate in the body’s first line of defense – innate lymphoid cells – also play a role in the maintenance of our tissues. A team Inserm from the Marseille-Luminy Immunology Center has just shown that, in mice, these cells are recruited into the brain after a stroke and there promote the functional recovery of the animals.

In mice, innate lymphoid cells (ILC) reduce the sequelae of an ischemic stroke, caused by the obstruction of a blood vessel: the animals show better motor skills when these immune players reach the site of the lesion . This is what has just been shown by a team from the Marseille-Luminy Immunology Center, led by Serge van de Pavert, who is studying the role of these recently described cells of the innate immune system. For the record, the innate immune system allows the body to respond quickly in the event of infection or injury. Its action is based on a set of specialized cells: dendritic cellspolynuclear, monocytesTHE macrophages… and therefore also the innate lymphoid cells. This first line of defense also makes it possible to trigger a second, that of adaptive immunity, which is specific to the intruder to be eliminated and is based on T lymphocytes and antibody produced by lymphocytes B.

ILCs are in a way a “non-specific” version of T lymphocytes. They differentiate from the same precursors as the latter, produce the same cocktails of cytokinesbut lack specific receptors for a antigenwhich characterize T lymphocytes. There are three subgroups of them, which present different cellular markers and whose presence varies from one tissue to another: the ILC1 which include the NK cells (pour Natural Killer), ILC2 and ILC3. ” Beyond their role in immune defence, innate lymphoid cells are involved in the functioning and remodeling of organs and tissues. As such, they are found in a large number of them. Depending on the circumstances, their presence can be beneficial or detrimental. », explains Serge van de Pavert. His team wanted to study them in the context of ischemic vascular accident: the brain is naturally poor in immune cells, but this event attracts a large number of immune cells: lymphocytes, monocytes, dendritic cells… The scientists wanted to know what so were the ILCs.

A ring of NK

For this work, the researchers used a mouse model in which an ischemic stroke can be induced experimentally. They looked for the presence of ILC in their brain using antibodies specific for markers present on the surface of the different subgroups, and this before and after the induction of the stroke. Result: the ILCs were absent before the event, but present after. In other words, stroke leads to the recruitment of these cells, in particular that of ILC1, including NK cells.

The team then looked at the distribution of these cells in the animals’ brains. Using imaging techniques, they discovered that they formed a ring around the lesion. Further experiments enabled them to identify the signaling pathway that attracts them to this site: the CXCL12/CXCR4 pathway. ” CXCL12 is a protein called chemokine, which controls migration several types of innate immune cells. She attaches herself to of the CXCR4 receptors, which are present on the surface of NK cells. By blocking this pathway, we prevent many of them from migrating into the brains of animals. », detail Serge van de Pavert.

Observations to be confirmed in humans

The functional role of ILCs recruited in response to stroke was then explored by subjecting the animals to a motor test, namely walking in balance on a small beam. Mice that had normal levels of NK cells in their brains after stroke were more adept than those in which recruitment of these cells had been blocked. ” We therefore find a beneficial effect of NK cells on functional recovery after stroke in this mouse model. This observation remains to be confirmed in humans, but it suggests that it could be interesting to know how to modulate the production and activity of these cells whose role is involved in other pathologies such as multiple sclerosis.explain Serge van de Pavert. One track is that of the intestinal flora, which we already know plays an important role in the regulation of immunity. An American team working on the modulation of NK cells has obtained an increase in their quantity in the body by modifying the composition of this microbiota » concludes Serge van de Pavert.

Serge van de Pavert is responsible for the team Development of the immune system at the Marseille-Luminy Immunology Center (CIML, unit 1104 Inserm/CNRS/Aix-Marseille University).

Source : S. Wang et coll. Brain endothelial CXCL12 attracts protective natural killer cells during ischemic stroke. Journal of Neuroinflammation du 11 janvier 2023 ; doi : 10.1186/s12974-023–02689‑x