title: Defects of immunoregulatory mechanisms in myasthenia gravis: role of IL-17.
abstract: Deficient immunoregulation is consistently observed in autoimmune diseases. Here, we summarize the abnormalities of the T cell response in autoimmune myasthenia gravis (MG) by focusing on activation markers, inflammatory features, and imbalance between the different T cell subsets, including Th17 and regulatory T cells (T(reg) cells). In the thymus from MG patients, T(reg) cell numbers are normal while their suppressive function is severely defective, and this defect could not be explained by contaminating effector CD127(low) T cells. A transcriptomic analysis of T(reg) cell and conventional T cell (T(conv) ; CD4(+) CD25(-) cells) subsets pointed out an upregulation of Th17-related genes in MG cells. Together with our previous findings of an inflammatory signature in the MG thymus and an overproduction of IL-1 and IL-6 by MG thymic epithelial cells (TEC), these data strongly suggest that T cell functions are profoundly altered in the thymic pathological environment. In this short review we discuss the mechanisms of chronic inflammation linked to the pathophysiology of MG disease.
authors.affiliation: Unité mixte de recherche, CNRS UMR/INSERM U/UPMC UM/AIM, Thérapie des maladies du muscle strié, Institut de Myologie, Paris, France.
authors.forename: Angeline
authors.initials: A
authors.lastname: Gradolatto
authors.forename: Dani
authors.initials: D
authors.lastname: Nazzal
authors.forename: Maria
authors.initials: M
authors.lastname: Foti
authors.forename: Jacky
authors.initials: J
authors.lastname: Bismuth
authors.forename: Frederique
authors.initials: F
authors.lastname: Truffault
authors.forename: Rozen
authors.initials: R
authors.lastname: Le Panse
authors.forename: Sonia
authors.initials: S
authors.lastname: Berrih-Aknin
mesh_terms: D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D009157:Myasthenia Gravis / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology
chemical_list: D007375:Interleukin-1; D020381:Interleukin-17; D015850:Interleukin-6