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 (Treg) 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 Treg 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 Treg cells that may be a general feature of autoimmunity.
- Experimental autoimmune myasthenia gravis (EAMG)
- Regulatory T cells