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

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....

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Autores principales:	Puspa Thapa, Bryce Manso, Ji Young Chung, Sinibaldo Romera Arocha, Hai-Hui Xue, Derek B. Sant’ Angelo, Virginia Smith Shapiro
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a955fde430764952a7afc41f1001ca19
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spelling	oai:doaj.org-article:a955fde430764952a7afc41f1001ca192021-12-02T16:08:24ZThe differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx110.1038/s41598-017-07365-82045-2322https://doaj.org/article/a955fde430764952a7afc41f1001ca192017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07365-8https://doaj.org/toc/2045-2322Abstract 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.Puspa ThapaBryce MansoJi Young ChungSinibaldo Romera ArochaHai-Hui XueDerek B. Sant’ AngeloVirginia Smith ShapiroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Puspa Thapa Bryce Manso Ji Young Chung Sinibaldo Romera Arocha Hai-Hui Xue Derek B. Sant’ Angelo Virginia Smith Shapiro The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1
description	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.
format	article
author	Puspa Thapa Bryce Manso Ji Young Chung Sinibaldo Romera Arocha Hai-Hui Xue Derek B. Sant’ Angelo Virginia Smith Shapiro
author_facet	Puspa Thapa Bryce Manso Ji Young Chung Sinibaldo Romera Arocha Hai-Hui Xue Derek B. Sant’ Angelo Virginia Smith Shapiro
author_sort	Puspa Thapa
title	The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1
title_short	The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1
title_full	The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1
title_fullStr	The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1
title_full_unstemmed	The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1
title_sort	differentiation of ror-γt expressing inkt17 cells is orchestrated by runx1
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a955fde430764952a7afc41f1001ca19
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The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1

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