NIP45 controls the magnitude of the type 2 T helper cell response
Year: 2010
Type: article
Abstract: 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. Whereas NIP45 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.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Emory University, Memorial Sloan-Kettering Cancer Center, Thailand Science Research and Innovation, National Institutes of Health, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke
Awards: The Role of Arginine Methyltransferases in Interferon Signaling, Cytokine Gene Regulation by Modification of Arginine Residues, Antigen Specific Therapy in CNS Autoimmune Diseases, NIP45: A Novel Nuclear Protein that Regulates IL-4, Mechanisms of Pulmonary Mast Cell Recruitment and Maturation, Harvard University Center for AIDS Research
OpenAlex ID: W2013408244