Experimental myasthenia gravis in Aire‐deficient mice: a link between Aire and regulatory T cells

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.