NIP45 controls the magnitude of the type 2 T helper cell response.

Proceedings of the National Academy of Sciences of the United States of America
John W FathmanKerri A Mowen

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.

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Citations

Aug 7, 2012·Molecular & Cellular Proteomics : MCP·Thomas UhlmannOreste Acuto
Oct 10, 2013·Briefings in Functional Genomics·Tapio LönnbergRiitta Lahesmaa
May 21, 2014·Nature Immunology·Kerri A Mowen, Michael David
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Sep 4, 2013·Applied Biochemistry and Biotechnology·Adriana Garibay-HernándezAlfredo Martinez
Apr 13, 2021·Frontiers in Immunology·Yves-Marie PersDanièle Noël

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