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. 2015 Dec;68(2 Pt B):484-9.
doi: 10.1016/j.molimm.2015.09.017. Epub 2015 Oct 17.

Cell-autonomous requirement for TCF1 and LEF1 in the development of Natural Killer T cells

Rosa Berga-Bolaños  1 , Wandi S Zhu  1 , Farrah C Steinke  2 , Hai-Hui Xue  2 , Jyoti Misra Sen  3
Affiliations

Cell-autonomous requirement for TCF1 and LEF1 in the development of Natural Killer T cells

V体育平台登录 - Rosa Berga-Bolaños et al. Mol Immunol. 2015 Dec.

Abstract

Natural killer T (NKT) cells develop from common CD4(+) CD8(+) thymocyte precursors. Transcriptional programs that regulate the development of NKT cells in the thymus development remain to be fully delineated. Here, we demonstrate a cell-intrinsic requirement for transcription factors TCF1 and LEF1 for the development of all subsets of NKT cells. Conditional deletion of TCF1 alone results in a substantial reduction in NKT cells. The remaining NKT cells are eliminated when TCF1 and LEF1 are both deleted VSports手机版. These data reveal an essential role for TCF1 and LEF1 in development of NKT cells. .

Keywords: LEF1; NKT cells; TCF1. V体育安卓版.

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Figures

FIGURE 1
FIGURE 1. TCF1 is expressed in NKT cells and controls the development of NKT cells
(A) Flow cytometry of TCF1 expression in total NKT cells and in NKT1, NKT2 and NKT17 subsets. Cells from TCF1/LEF1-cDKO are shown as a negative control in shaded grey. Data are representative of three mice. Flow cytometry from a representative experiment showing frequency of total NKT (B) and mature NKT1, NKT2 and NKT17 cells gated by two different strategies as shown (C) from control and TCF1-cKO mice. Graphs show cell numbers gated from each population from thymus, (B, C), spleen and liver (D) of control and TCF1-cKO mice (n ≥ 3, mean ± sem). Numbers over dot plots in (B) refer to total thymocyte cell numbers. * P<.05; ** P<.01; *** P<.001.
FIGURE 2
FIGURE 2. LEF1 is expressed in NKT cells and participates in the development of NKT cells
(A) Flow cytometry of LEF1 expression in total NKT cells and in NKT1, NKT2 and NKT17 subsets. Cells from TCF1/LEF1-cDKO are shown as a negative control in shaded grey. Data are representative of three mice. (B) A representative flow plot showing frequency of total NKT cells from control (n=3), LEF1-cKO (n=2), TCF1-cKO (n=2), TCF1/LEF1-cDKO (n=5) and CD1d-KO (n=3) mice. Graph shows total thymic NKT cell numbers from each experimental group (mean ± sem). (C) Flow cytometry plot showing frequency of mature NKT cell types from control and TCF1/LEF1-cDKO mice. Graphs below show cell numbers of various NKT cell populations from thymus (n ≥ 3, mean ± sem). (D) Representative plots showing frequency of NKT cells (top) and NKT0 cells (CD1d-tet+TCRβ+CD24+) (bottom) from control, LEF1-cKO, TCF1-cKO and TCF1/LEF1-cDKO mice. Also shown is a representative plot of TCF1/LEF1-cDKO mouse stained with unloaded-tetramer as isotype control for CD1d-tet. Frequency numbers presented in NKT0 plots represent percentage of NKT cells. * P<.05; ** P<.01; *** P<.001.
FIGURE 3
FIGURE 3. TCF1 and LEF1 control the development of NKT cells in a cell-intrinsic manner
Flow cytometry of a bone-marrow chimera experiment analyzed 13 weeks post-transplantation. CD45.1+ recipient C57BL/6.SJL irradiated mice were transplanted with CD45.2+ cells from control, TCF1-cKO or TCF1/LEF1-cDKO mice. Thymic cells gated on CD45.2+ cells (donor) were further analyzed. Representative experiment shows frequency of total NKT (A), NKT0 (B) and mature NKT subsets (C) from control, TCF1-cKO and TCF1/LEF1-cDKO donor cells. Graphs show cell numbers gated from each population from thymus of recipient that received donor control (n=2), TCF1-cKO (n=2) or TCF1/LEF1-cDKO mice (n = 3) (mean ± st dev). * P<.05; ** P<.01; *** P<.001.
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