Fli-1 regulates the DN2 to DN3 thymocyte transition and promotes γδ T-cell commitment by enhancing TCR signal strength.

Autor: Smeets MF; Haematology and Leukaemia Unit, St. Vincent's Institute, Fitzroy, Victoria, Australia., Wiest DL, Izon DJ
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2014 Sep; Vol. 44 (9), pp. 2617-24. Date of Electronic Publication: 2014 Jul 24.
DOI: 10.1002/eji.201444442
Abstrakt: Friend leukemia integration 1 (Fli-1) is a member of the Ets transcription factor family and is expressed during T-cell development; however, the role Fli-1 plays in early T-cell differentiation has not been elucidated. In this report, we demonstrate that in mouse, Fli-1 overexpression retards the CD4(-) CD8(-) double-negative (DN) to CD4(+) CD8(+) double-positive (DP) transition by deregulating normal DN thymocyte development. Specifically, Fli-1 expression moderates the DN2 and DN3 developmental transitions. We further show that Fli-1 overexpression partially mimics strong TCR signals in developing DN thymocytes and thereby enhances γδ T-cell development. Conversely, Fli-1 knockdown by small hairpin RNA reverses the lineage bias from γδ T cells and directs DN cells to the αβ lineage by attenuating TCR signaling. Therefore, Fli-1 plays a critical role in both the DN2 to DN3 transition and αβ/γδ lineage commitment.
Competing Interests: The authors declare no financial or commercial conflict of interest.
(© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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