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Nat Immunol. 2016 Jul;17(7):834-43. doi: 10.1038/ni.3461. Epub 2016 May 23.

Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation.

Author information

1
Department of Biological Sciences, University of California San Diego, La Jolla, California, USA.
2
Division of Vaccine Discovery, La Jolla Institute for Allergy &Immunology, La Jolla, California, USA.
3
Division of Signaling and Gene Expression, La Jolla Institute for Allergy &Immunology, La Jolla, California, USA.
4
Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA.
5
Department of Medicine, University of California San Diego, La Jolla, California, USA.

Abstract

The differentiation of helper T cells into effector subsets is critical to host protection. Transcription factors of the E-protein and Id families are important arbiters of T cell development, but their role in the differentiation of the TH1 and TFH subsets of helper T cells is not well understood. Here, TH1 cells showed more robust Id2 expression than that of TFH cells, and depletion of Id2 via RNA-mediated interference increased the frequency of TFH cells. Furthermore, TH1 differentiation was blocked by Id2 deficiency, which led to E-protein-dependent accumulation of effector cells with mixed characteristics during viral infection and severely impaired the generation of TH1 cells following infection with Toxoplasma gondii. The TFH cell-defining transcriptional repressor Bcl6 bound the Id2 locus, which provides a mechanism for the bimodal Id2 expression and reciprocal development of TH1 cells and TFH cells.

PMID:
27213691
PMCID:
PMC4915968
DOI:
10.1038/ni.3461
[Indexed for MEDLINE]
Free PMC Article

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