The susceptibility of Aire-/- mice to experimental myasthenia gravis involves alterations in regulatory T cells

Revital Aricha, Tali Feferman, Hamish S. Scott, Miriam C. Souroujon, Sonia Berrih-Aknin, Sara Fuchs

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים


The autoimmune regulator (Aire) is involved in the prevention of autoimmunity by promoting thymic expression of tissue restricted antigens which leads to elimination of self-reactive T cells. We found that Aire knockout (KO) mice as well as mouse strains that are susceptible to experimental autoimmune myasthenia gravis (EAMG) have lower thymic expression of acetylcholine receptor (AChR- the main autoantigen in MG), compared to wild type (WT) mice and EAMG-resistant mouse strains, respectively. We demonstrated that Aire KO mice have a significant and reproducible lower frequency of CD4+Foxp3+ cells and a higher expression of Th17 markers in their thymus, compared to wild type (WT) mice. These findings led us to expect that Aire KO mice would display increased susceptibility to EAMG. Surprisingly, when EAMG was induced in young (2 month-old) mice, EAMG was milder in Aire KO than in WT mice for several weeks until the age of about 5 months. However, when EAMG was induced in relatively aged (6 month-old) mice, Aire KO mice presented higher disease severity than WT controls. This age-related change in susceptibility to EAMG correlated with an elevated proportion of Treg cells in the spleens of young but not old KO, compared to WT mice, suggesting a role for peripheral Treg cells in the course of disease. Our observations point to a possible link between Aire and Treg cells and suggest an involvement for both in the pathogenesis of myasthenia.

שפה מקוריתאנגלית
עמודים (מ-עד)16-24
מספר עמודים9
כתב עתJournal of Autoimmunity
מספר גיליון1
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - פבר׳ 2011

הערה ביבליוגרפית

Funding Information:
Supported by grants from The Muscular Dystrophy Association of America (MDA) , The Association Francaise Contre les Myopathies (AFM) , The European Commission (FIGHT-MG, contract # FP7 HEALTH-2009-242-210 .), The National Health and Medical Research Council of Australia ( 171601, 461204, 257501, 264573 and 406700 ), and Eurothymaide , of the EU (contract # LSHB-CT-2003-503410 ).

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