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Experimental myasthenia gravis in Aire‐deficient mice: a link between Aire and regulatory T cells
Author(s) -
Aricha Revital,
Feferman Tali,
BerrihAknin Sonia,
Fuchs Sara,
Souroujon Miriam C.
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06843.x
Subject(s) - autoimmune regulator , myasthenia gravis , autoimmunity , autoimmune disease , immunology , regulator , biology , endocrinology , medicine , immune system , antibody , gene , genetics
Aire (autoimmune regulator) has a key role in the establishment of tolerance to autoantigens. Aire −/− mice present decreased thymic expression of AChR, significantly lower frequencies of regulatory T (T reg ) cells, and higher expression of Th17 markers, compared to controls. We therefore predicted that Aire −/− mice would be more susceptible to induction of experimental autoimmune myasthenia gravis (EAMG). However, when EAMG was induced in young mice, Aire −/− mice presented a milder disease that wild‐type (WT) controls. In contrast, when EAMG was induced in older mice, Aire −/− mice were more severely affected than WT mice. The relative resistance to EAMG in young Aire −/− mice correlated with increased numbers of T reg cells in their spleens compared to young controls. A similar age‐related susceptibility was also observed when EAE was induced in Aire −/− mice, suggesting an age‐related link among Aire, disease susceptibility, and peripheral T reg cells that may be a general feature of autoimmunity.