Gadd45 proteins: relevance to aging, longevity and age-related pathologies.
The number of effector T cells is controlled by proliferation and programmed cell death. Loss of these controls on self-destructive effector T cells may precipitate autoimmunity. Here, we show that two members of the growth arrest and DNA damage-inducible ( Gadd45 ) family, and , are critical in the development of pathogenic effector T cells. CD4 T cells lacking Gadd45 can rapidly expand and invade the central nervous system in response to myelin immunization, provoking an exacerbated and prolonged autoimmune encephalomyelitis in mice. Importantly, mice with compound deficiency in Gadd45 and Gadd45 spontaneously developed signs of autoimmune lymphoproliferative syndrome and systemic lupus erythematosus. Our findings therefore identify the Gadd45 /Gadd45 -mediated control of effector autoimmune lymphocytes as an attractive novel target for autoimmune disease therapy.