HEB is required for the specification of fetal IL-17-producing γδ T cells.
Nat Commun
; 8(1): 2004, 2017 12 08.
Article
in En
| MEDLINE
| ID: mdl-29222418
ABSTRACT
IL-17-producing γδ T (γδT17) cells are critical components of the innate immune system. However, the gene networks that control their development are unclear. Here we show that HEB (HeLa E-box binding protein, encoded by Tcf12) is required for the generation of a newly defined subset of fetal-derived CD73- γδT17 cells. HEB is required in immature CD24+CD73- γδ T cells for the expression of Sox4, Sox13, and Rorc, and these genes are repressed by acute expression of the HEB antagonist Id3. HEB-deficiency also affects mature CD73+ γδ T cells, which are defective in RORγt expression and IL-17 production. Additionally, the fetal TCRγ chain repertoire is altered, and peripheral Vγ4 γδ T cells are mostly restricted to the IFNγ-producing phenotype in HEB-deficient mice. Therefore, our work identifies HEB-dependent pathways for the development of CD73+ and CD73- γδT17 cells, and provides mechanistic evidence for control of the γδT17 gene network by HEB.
Full text:
1
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Developmental
/
Fetal Development
/
Basic Helix-Loop-Helix Transcription Factors
/
Intraepithelial Lymphocytes
/
Immunity, Innate
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Year:
2017
Type:
Article