Essential function for the kinase TAK1 in innate and adaptive immune responses.
Transforming growth factor-beta-activated kinase 1 (TAK1) has been linked to interleukin 1 receptor and tumor necrosis factor receptor signaling. Here we generated mouse strains with conditional expression of a Map3k7 allele encoding part of TAK1. TAK1-deficient embryonic fibroblasts demonstrated loss of responses to interleukin 1beta and tumor necrosis factor. Studies of mice with B cell-specific TAK1 deficiency showed that TAK1 was indispensable for cellular responses to Toll-like receptor ligands, CD40 and B cell receptor crosslinking. In addition, antigen-induced immune responses were considerably impaired in mice with B cell-specific TAK1 deficiency. TAK1-deficient cells failed to activate transcription factor NF-kappaB and mitogen-activated protein kinases in response to interleukin 1beta, tumor necrosis factor and Toll-like receptor ligands. However, TAK1-deficient B cells were able to activate NF-kappaB but not the kinase Jnk in response to B cell receptor stimulation. These results collectively indicate that TAK1 is key in the cellular response to a variety of stimuli.
Pubmed ID: 16186825 RIS Download
Animals | Antigens, CD40 | B-Lymphocytes | Embryo, Mammalian | Fibroblasts | Gene Deletion | Immunity, Innate | Interleukin-17 | Lymphopoiesis | MAP Kinase Kinase Kinases | Membrane Glycoproteins | Mice | Mice, Mutant Strains | NF-kappa B | Receptors, Antigen, B-Cell | Receptors, Cell Surface | Toll-Like Receptors | Tumor Necrosis Factor-alpha