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

Publication ,  Journal Article
Fathman, JW; Gurish, MF; Hemmers, S; Bonham, K; Friend, DS; Grusby, MJ; Glimcher, LH; Mowen, KA
Published in: Proc Natl Acad Sci U S A
February 23, 2010

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.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 23, 2010

Volume

107

Issue

8

Start / End Page

3663 / 3668

Location

United States

Related Subject Headings

  • Trichinellosis
  • Trichinella spiralis
  • Th2 Cells
  • Protein-Arginine N-Methyltransferases
  • Promoter Regions, Genetic
  • Nuclear Proteins
  • NFATC Transcription Factors
  • Mice, Mutant Strains
  • Mice
  • Methylation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fathman, J. W., Gurish, M. F., Hemmers, S., Bonham, K., Friend, D. S., Grusby, M. J., … Mowen, K. A. (2010). NIP45 controls the magnitude of the type 2 T helper cell response. Proc Natl Acad Sci U S A, 107(8), 3663–3668. https://doi.org/10.1073/pnas.0914700107
Fathman, John W., Michael F. Gurish, Saskia Hemmers, Kevin Bonham, Daniel S. Friend, Michael J. Grusby, Laurie H. Glimcher, and Kerri A. Mowen. “NIP45 controls the magnitude of the type 2 T helper cell response.Proc Natl Acad Sci U S A 107, no. 8 (February 23, 2010): 3663–68. https://doi.org/10.1073/pnas.0914700107.
Fathman JW, Gurish MF, Hemmers S, Bonham K, Friend DS, Grusby MJ, et al. NIP45 controls the magnitude of the type 2 T helper cell response. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3663–8.
Fathman, John W., et al. “NIP45 controls the magnitude of the type 2 T helper cell response.Proc Natl Acad Sci U S A, vol. 107, no. 8, Feb. 2010, pp. 3663–68. Pubmed, doi:10.1073/pnas.0914700107.
Fathman JW, Gurish MF, Hemmers S, Bonham K, Friend DS, Grusby MJ, Glimcher LH, Mowen KA. NIP45 controls the magnitude of the type 2 T helper cell response. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3663–3668.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 23, 2010

Volume

107

Issue

8

Start / End Page

3663 / 3668

Location

United States

Related Subject Headings

  • Trichinellosis
  • Trichinella spiralis
  • Th2 Cells
  • Protein-Arginine N-Methyltransferases
  • Promoter Regions, Genetic
  • Nuclear Proteins
  • NFATC Transcription Factors
  • Mice, Mutant Strains
  • Mice
  • Methylation