Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation

Nat Immunol. 2016 May 23. doi: 10.1038/ni.3461. [Epub ahead of print]

Shaw LA1, Bélanger S2, Omilusik KD1, Cho S1, Scott-Browne JP3, Nance JP2, Goulding J1, Lasorella A4, Lu LF1, Crotty S2,5, Goldrath AW1.

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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

 

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