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.