Open AccessNIP45 controls the magnitude of the type 2 T helper cell response
Author(s) -
John W. Fathman,
Michael F. Gurish,
Saskia Hemmers,
Kevin S. Bonham,
Daniel S. Friend,
Michael J. Grusby,
Laurie H. Glimcher,
Kerri Mowen
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0914700107
Subject(s) - nfat , transcription factor , biology , t cell , enhancer , histone methyltransferase , microbiology and biotechnology , protein arginine methyltransferase 5 , methylation , protein methylation , regulation of gene expression , immune system , methyltransferase , gene , genetics
Nuclear factor of activated T cell (NFAT) transcription factors are key regulators of gene transcription within immune cells. The NFAT-interacting protein, (NIP45), augments NFAT-driven IL-4 expression by a mechanism that relies on arginine methylation. To establish the function of NIP45 in vivo, we generated mice with a targeted deletion of the gene encoding this cofactor.NIP45 -deficient T helper cells displayed profound defects in the expression of NFAT-regulated cytokine genes, including IL-4. WhereasNIP45 deficiency does not interfere with T helper cell NFAT activation or lineage-specific transcription-factor expression, NIP45 acts as an enhancer for the assembly of protein arginine methyltransferase 1 and the protein arginine methyltransferase 1-linked histone 4 arginine 3 methylation with the IL-4 promoter. Our study reveals an essential role for NIP45 in promoting robust cytokine expression in vivo, which is required for the efficient handling of parasites. We propose that NIP45 acts as a molecular rheostat serving to amplify the type-2 immune response.