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Smeets MF , Wiest DL , Izon DJ
Fli-1 regulates the DN2 to DN3 thymocyte transition and promotes gammadelta T-cell commitment by enhancing TCR signal strength
Eur J Immunol. 2014 Sep;44(9) :2617-24
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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 gammadelta T-cell development. Conversely, Fli-1 knockdown by small hairpin RNA reverses the lineage bias from gammadelta T cells and directs DN cells to the alphabeta lineage by attenuating TCR signaling. Therefore, Fli-1 plays a critical role in both the DN2 to DN3 transition and alphabeta/gammadelta lineage commitment.
Smeets, Monique F M A Wiest, David L Izon, David J ENG Research Support, Non-U.S. Gov't Germany 2014/06/18 06:00 Eur J Immunol. 2014 Sep;44(9):2617-24. doi: 10.1002/eji.201444442. Epub 2014 Jul 24.