Double-edged Gadd45

On page 1341, Liu and colleagues report that members of the growth arrest and DNA damage-inducible (Gadd45) family help both start and stop effector T cell activity—critically acting to quench autoimmune T cells gone haywire.The Gadd45 family is best known and named for arresting growth of stressed cells by binding cell cycle machinery. In immune cells, the Gadd45 proteins directly bind MEKK4, promoting its activation of the p38 and JNK MAP kinases. Gadd45β and Gadd45γ's activation of p38 is essential for jump-starting T helper (Th) type 1 cell differentiation via production of interferon-γ (IFNγ).

Previously, this group demonstrated that mice lacking Gadd45β mount a much reduced Th1 response against intracellular pathogens like Listeria monocytogenes. The diminished IFNγ-producing cells suggested that Gadd45β helps T cells differentiate. But now their recent studies suggest an additional...