MAPK signaling is important for T lymphocyte development, homeostasis, and effector responses. To better understand the role of Mekk1 (encoded by Map3k1) in T cells, we conditionally deleted Map3k1 in Lck Cre/+ Map3k1 f/f mice, and these display larger iNKT cell populations within the liver, spleen, and bone marrow. Mekk1 signaling controls splenic and liver iNKT cell expansion in response to glycolipid antigen. Lck Cre/+ Map3k1 f/f mice have enhanced liver damage in response to glycolipid antigen. Mekk1 regulates Jnk activation in iNKT cells and binds and transfers Lys63-linked poly-ubiquitin onto Carma1. Map3k1 is critical for the regulation of p27 Kip1 (encoded by Cdkn1b).
Suddason et al. use a T-cell-specific deletion of Map3k1 to show that Mekk1 regulates TCR-dependent Jnk activation and Cdkn1b expression to drive proliferation in response to antigen.