The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production.
Yoshida H., Nishina H., Takimoto H., Marengère LE., Wakeham AC., Bouchard D., Kong YY., Ohteki T., Shahinian A., Bachmann M., Ohashi PS., Penninger JM., Crabtree GR., Mak TW.
NF-ATc1 is a member of a family of genes that encodes the cytoplasmic component of the nuclear factor of activated T cells (NF-AT). In activated T cells, nuclear NF-AT binds to the promoter regions of multiple cytokine genes and induces their transcription. The role of NF-ATc1 was investigated in recombination activating gene-1 (RAG-1)-deficient blastocyst complementation assays using homozygous NF-ATc1-/- mutant ES cell lines. NF-ATc1-/-/RAG-1-/- chimeric mice showed reduced numbers of thymocytes and impaired proliferation of peripheral lymphocytes, but normal production of IL-2. Induction in vitro of Th2 responses, as demonstrated by a decrease in IL-4 and IL-6 production, was impaired in mutant T cells. These data indicate that NF-ATc1 plays roles in the development of T lymphocytes and in the differentiation of the Th2 response.