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Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development.
- Source :
- Nature; 3/27/2014, Vol. 507 Issue 7493, p513-518, 6p
- Publication Year :
- 2014
-
Abstract
- In immune responses, activated T cells migrate to B-cell follicles and develop into follicular T-helper (T<subscript>FH</subscript>) cells, a recently identified subset of CD4<superscript>+</superscript> T cells specialized in providing help to B lymphocytes in the induction of germinal centres. Although Bcl6 has been shown to be essential in T<subscript>FH</subscript>-cell function, it may not regulate the initial migration of T cells or the induction of the T<subscript>FH</subscript> program, as exemplified by C-X-C chemokine receptor type 5 (CXCR5) upregulation. Here we show that expression of achaete-scute homologue 2 (Ascl2)-a basic helix-loop-helix (bHLH) transcription factor-is selectively upregulated in T<subscript>FH</subscript> cells. Ectopic expression of Ascl2 upregulates CXCR5 but not Bcl6, and downregulates C-C chemokine receptor 7 (CCR7) expression in T cells in vitro, as well as accelerating T-cell migration to the follicles and T<subscript>FH</subscript>-cell development in vivo in mice. Genome-wide analysis indicates that Ascl2 directly regulates T<subscript>FH</subscript>-related genes whereas it inhibits expression of T-helper cell 1 (T<subscript>H</subscript>1) and T<subscript>H</subscript>17 signature genes. Acute deletion of Ascl2, as well as blockade of its function with the Id3 protein in CD4<superscript>+</superscript> T cells, results in impaired T<subscript>FH</subscript>-cell development and germinal centre response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances T<subscript>FH</subscript>-cell generation. Thus, Ascl2 directly initiates T<subscript>FH</subscript>-cell development. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 507
- Issue :
- 7493
- Database :
- Complementary Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 97424693
- Full Text :
- https://doi.org/10.1038/nature12910