TY - JOUR
T1 - The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1
AU - Thapa, Puspa
AU - Manso, Bryce
AU - Chung, Ji Young
AU - Romera Arocha, Sinibaldo
AU - Xue, Hai Hui
AU - Angelo, Derek B.Sant
AU - Shapiro, Virginia Smith
N1 - Funding Information:
We thank the National Institute of Health (NIH) Tetramer Core Facility for generously providing us with PE and BV421 conjugated CD1d tetramers. We thank Dr. Nobuo Sakaguchi (Kumamoto University, Kumamoto, Japan) for Rag1-GFP knock in mice. We thank Dr. Al Singer (NCI, Bethesda, MD) for the IL-7Rá Tg mice. We thank all laboratory members of V.S.S. and Dr. Kay Medina (Mayo Clinic) for helpful discussions. This work was supported by NIH grants AI1069031 and AI083279 to V.S.S. and AI121080 to H-H.X.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - iNKT cells are a unique lineage of T cells that recognize glycolipid presented by CD1d. In the thymus, they differentiate into iNKT1, iNKT2 and iNKT17 effector subsets, characterized by preferential expression of Tbet, Gata3 and ROR-γt and production of IFN-γ, IL-4 and IL-17, respectively. We demonstrate that the transcriptional regulator Runx1 is essential for the generation of ROR-γt expressing iNKT17 cells. PLZF-cre Runx1 cKO mice lack iNKT17 cells in the thymus, spleen and liver. Runx1-deficient iNKT cells have altered expression of several genes important for iNKT17 differentiation, including decreased expression of IL-7Rα, BATF and c-Maf and increased expression of Bcl11b and Lef1. However, reduction of Lef1 expression or introduction of an IL-7Rα transgene is not sufficient to correct the defect in iNKT17 differentiation, demonstrating that Runx1 is a key regulator of several genes required for iNKT17 differentiation. Loss of Runx1 leads to a severe decrease in iNKT cell numbers in the thymus, spleen and liver. The decrease in cell number is due to a combined decrease in proliferation at Stage 1 during thymic development and increased apoptosis. Thus, we describe a novel role of Runx1 in iNKT cell development and differentiation, particularly in orchestrating iNKT17 differentiation.
AB - iNKT cells are a unique lineage of T cells that recognize glycolipid presented by CD1d. In the thymus, they differentiate into iNKT1, iNKT2 and iNKT17 effector subsets, characterized by preferential expression of Tbet, Gata3 and ROR-γt and production of IFN-γ, IL-4 and IL-17, respectively. We demonstrate that the transcriptional regulator Runx1 is essential for the generation of ROR-γt expressing iNKT17 cells. PLZF-cre Runx1 cKO mice lack iNKT17 cells in the thymus, spleen and liver. Runx1-deficient iNKT cells have altered expression of several genes important for iNKT17 differentiation, including decreased expression of IL-7Rα, BATF and c-Maf and increased expression of Bcl11b and Lef1. However, reduction of Lef1 expression or introduction of an IL-7Rα transgene is not sufficient to correct the defect in iNKT17 differentiation, demonstrating that Runx1 is a key regulator of several genes required for iNKT17 differentiation. Loss of Runx1 leads to a severe decrease in iNKT cell numbers in the thymus, spleen and liver. The decrease in cell number is due to a combined decrease in proliferation at Stage 1 during thymic development and increased apoptosis. Thus, we describe a novel role of Runx1 in iNKT cell development and differentiation, particularly in orchestrating iNKT17 differentiation.
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U2 - 10.1038/s41598-017-07365-8
DO - 10.1038/s41598-017-07365-8
M3 - Article
C2 - 28765611
AN - SCOPUS:85026741420
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 7018
ER -