Flagship projects

Role of innate immune cells in myasthenia gravis

MG-Innate: better understanding the role of γδ T cells in myasthenia gravis

The project explores the role of certain innate immune cells, in particular gamma delta T lymphocytesC’est une catégorie de globules blancs. Ces petites cellules au noyau arrondi et volumineux sont impliquées dans les aspects spécifiques des réactions immunitaires. Il existe deux catégories de lymphocytes les lymphocytes B (qui secrètent les anticorps) et les lymphocytes T. (γδ T cells), in autoimmune myasthenia gravis. These cells, still very little studied in this disease, may contribute to the immune dysregulation that disrupts communication between the nerve and the muscle and leads to muscle weakness.

Scientific challenge

Myasthenia gravis is generally studied from the perspective of adaptive immunity, which is responsible for producing the autoantibodies that block the neuromuscular junction. But innate immunity, the body’s first line of defence, may play an essential role in the onset of immune dysregulation, particularly in the thymus. Understanding how γδ T cells are involved in these mechanisms could shed light not only on myasthenia gravis, but also on other autoimmune diseases in which the interactions between innate and adaptive immunity remain poorly understood.

Key questions to unravel

The work aims to determine:

how γδ T cells are altered in myasthenia gravis;
what specific features they show depending on the form of the disease;
how they interact with the other cells of the thymus and of the immune system;
whether they contribute to the dysregulation that leads to the attack on the muscle.

The aim is to identify immune mechanisms that remain unexplored and could become new therapeutic targets.

Scientific and methodological approach

The researchers will analyse:

patient samples (blood, thymus, muscle) from a unique collection built up by the team;
the characteristics of γδ T cells in different forms of myasthenia gravis;
the links between thymic abnormalities (inflammationRéaction non spécifique suscitée par un agent pathogène., thymoma) and muscle involvement;
experimental models used to study the role of these cells in immune dysregulation.

This work relies on close collaboration between researchers, engineers, clinicians and specialists in immunology and myology.

Autoimmune diseases share many common mechanisms. What we discover in myasthenia gravis may therefore be of broader interest for understanding other autoimmune diseases. This work also sheds light on mechanisms that occur upstream of muscle involvement, complementing research into the consequences of the disease at the muscle level.
Rozen Le Panse, research team leader at the Center of Research in Myology

Expected impact on research and clinical practice

A better understanding of the role of γδ T cells could:

explain why some patients respond less well to current treatments;
open the way to more targeted therapies acting on specific immune mechanisms;
allow the repurposing of drugs already used in other autoimmune diseases;
contribute to more personalised care, based on the immune profiles of patients.

The knowledge generated could also shed light on other autoimmune diseases in which the interactions between innate and adaptive immunity play a key role.