The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1

Puspa Thapa, Bryce Manso, Ji Young Chung, Sinibaldo Romera Arocha, Hai Hui Xue, Derek B.Sant Angelo, Virginia M Shapiro

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number7018
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Natural Killer T-Cells
Thymus Gland
Spleen
Cell Count
Interleukin-17
Liver
Glycolipids
Regulator Genes
Transgenes
Interleukin-4
Cell Differentiation
Apoptosis
T-Lymphocytes
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

Thapa, P., Manso, B., Chung, J. Y., Romera Arocha, S., Xue, H. H., Angelo, D. B. S., & Shapiro, V. M. (2017). The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1. Scientific Reports, 7(1), [7018]. https://doi.org/10.1038/s41598-017-07365-8

The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1. / Thapa, Puspa; Manso, Bryce; Chung, Ji Young; Romera Arocha, Sinibaldo; Xue, Hai Hui; Angelo, Derek B.Sant; Shapiro, Virginia M.

In: Scientific Reports, Vol. 7, No. 1, 7018, 01.12.2017.

Research output: Contribution to journalArticle

Thapa, P, Manso, B, Chung, JY, Romera Arocha, S, Xue, HH, Angelo, DBS & Shapiro, VM 2017, 'The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1', Scientific Reports, vol. 7, no. 1, 7018. https://doi.org/10.1038/s41598-017-07365-8
Thapa P, Manso B, Chung JY, Romera Arocha S, Xue HH, Angelo DBS et al. The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1. Scientific Reports. 2017 Dec 1;7(1). 7018. https://doi.org/10.1038/s41598-017-07365-8
Thapa, Puspa ; Manso, Bryce ; Chung, Ji Young ; Romera Arocha, Sinibaldo ; Xue, Hai Hui ; Angelo, Derek B.Sant ; Shapiro, Virginia M. / The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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