Tissue inflammation in several autoimmune diseases, including SLE and MS, has been linked to an imbalance of IL-17–producing Th (Th17) cells and Tregs; however, the factors that promote Th17-driven autoimmunity are unclear. Here, we present evidence that the calcium/calmodulin-dependent protein kinase IV (CaMK4) is increased and required during Th17 cell differentiation. Isolation of naive T cells from a murine model of lupus revealed increased levels of CaMK4 following stimulation with Th17-inducing cytokines but not following Treg, Th1, or Th2 induction. Furthermore, naive T cells from mice lacking CaMK4 did not produce IL-17. Genetic or pharmacologic inhibition of CaMK4 decreased the frequency of IL-17–producing T cells and ameliorated EAE and lupus-like disease in murine models. Inhibition of CaMK4 reduced
Tomohiro Koga, Christian M. Hedrich, Masayuki Mizui, Nobuya Yoshida, Kotaro Otomo, Linda A. Lieberman, Thomas Rauen, José C. Crispín, George C. Tsokos
CaMK4 is induced during Th17 differentiation.