Transcriptional Complexes Formed by NFAT Dimers Regulate the Induction of T Cell Tolerance

DSpace/Manakin Repository

Transcriptional Complexes Formed by NFAT Dimers Regulate the Induction of T Cell Tolerance

Citable link to this page

. . . . . .

Title: Transcriptional Complexes Formed by NFAT Dimers Regulate the Induction of T Cell Tolerance
Author: Soto-Nieves, Noemi; Puga, Irene; Abe, Brian T.; Bandyopadhyay, Sanmay; Baine, Ian; Macian, Fernando; Rao, Anjana

Note: Order does not necessarily reflect citation order of authors.

Citation: Soto-Nieves, Noemi, Irene Puga, Brian T. Abe, Sanmay Bandyopadhyay, Ian Baine, Anjana Rao, and Fernando Macian. 2009. Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance. The Journal of Experimental Medicine 206(4): 867-876.
Full Text & Related Files:
Abstract: In T cells, anergy can be induced after T cell receptor engagement in the absence of costimulation. Under these conditions, the expression of a specific set of anergy-associated genes is activated. Several lines of evidence suggest that nuclear factor of activated T cells (NFAT) proteins may regulate the expression of many of those genes; however, the nature of the complexes responsible for the induction of this new program of gene expression is unknown. Here, we show that transcriptional complexes formed by NFAT homodimers are directly responsible for the activation of at least two anergy-inducing genes, Grail and Caspase3. Our data shows that Grail expression is activated by direct binding of NFAT dimers to the Grail promoter at two different sites. Consequently, a mutant NFAT protein with impaired ability to dimerize is not able to induce an unresponsive state in T cells. Our results not only identify a new biological function for NFAT dimers but also reveal the different nature of NFAT-containing complexes that induce anergy versus those that are activated during a productive immune response. These data also establish a basis for the design of immunomodulatory strategies that specifically target each type of complex.
Published Version: doi:10.1084/jem.20082731
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715123/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4551467

Show full Dublin Core record

This item appears in the following Collection(s)

  • FAS Scholarly Articles [7219]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University
 
 

Search DASH


Advanced Search
 
 

Submitters