Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells.

CD4(+)Foxp3(+) T regulatory cells (Tregs) display phenotypic and functional plasticity that is regulated by cytokines and other immune cells. Previously, we determined that during co-culture with CD4(+)CD25(-) T cells and antigen presenting cells, Tregs produced IL-17. Here, we investigated the mech...

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Main Authors: Lequn Li, Nikolaos Patsoukis, Victoria Petkova, Vassiliki A Boussiotis
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3440330?pdf=render
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author Lequn Li
Nikolaos Patsoukis
Victoria Petkova
Vassiliki A Boussiotis
author_facet Lequn Li
Nikolaos Patsoukis
Victoria Petkova
Vassiliki A Boussiotis
author_sort Lequn Li
collection DOAJ
description CD4(+)Foxp3(+) T regulatory cells (Tregs) display phenotypic and functional plasticity that is regulated by cytokines and other immune cells. Previously, we determined that during co-culture with CD4(+)CD25(-) T cells and antigen presenting cells, Tregs produced IL-17. Here, we investigated the mechanisms underlying the differentiation of IL-17-producing Treg (Tr17) cells and their molecular and functional properties. We determined that during stimulation via TCR/CD3 and CD28, the combination of IL-1β and IL-2 was necessary and sufficient for the generation of Tr17 cells. Tr17 cells expressed Runx1 transcription factor, which was required for sustained expression of Foxp3 and RORγt and for production of IL-17. Surprisingly, Tr17 cells also expressed Runx3, which regulated transcription of perforin and granzyme B thereby mediating cytotoxic activity. Our studies indicate that Tr17 cells concomitantly express Foxp3, RORγt, Runx1 and Runx3 and are capable of producing IL-17 while mediating potent suppressive and cytotoxic function.
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spelling doaj.art-81d22d3945244c2a9bedd7a5b36732bb2022-12-21T17:30:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4511510.1371/journal.pone.0045115Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells.Lequn LiNikolaos PatsoukisVictoria PetkovaVassiliki A BoussiotisCD4(+)Foxp3(+) T regulatory cells (Tregs) display phenotypic and functional plasticity that is regulated by cytokines and other immune cells. Previously, we determined that during co-culture with CD4(+)CD25(-) T cells and antigen presenting cells, Tregs produced IL-17. Here, we investigated the mechanisms underlying the differentiation of IL-17-producing Treg (Tr17) cells and their molecular and functional properties. We determined that during stimulation via TCR/CD3 and CD28, the combination of IL-1β and IL-2 was necessary and sufficient for the generation of Tr17 cells. Tr17 cells expressed Runx1 transcription factor, which was required for sustained expression of Foxp3 and RORγt and for production of IL-17. Surprisingly, Tr17 cells also expressed Runx3, which regulated transcription of perforin and granzyme B thereby mediating cytotoxic activity. Our studies indicate that Tr17 cells concomitantly express Foxp3, RORγt, Runx1 and Runx3 and are capable of producing IL-17 while mediating potent suppressive and cytotoxic function.http://europepmc.org/articles/PMC3440330?pdf=render
spellingShingle Lequn Li
Nikolaos Patsoukis
Victoria Petkova
Vassiliki A Boussiotis
Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells.
PLoS ONE
title Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells.
title_full Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells.
title_fullStr Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells.
title_full_unstemmed Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells.
title_short Runx1 and Runx3 are involved in the generation and function of highly suppressive IL-17-producing T regulatory cells.
title_sort runx1 and runx3 are involved in the generation and function of highly suppressive il 17 producing t regulatory cells
url http://europepmc.org/articles/PMC3440330?pdf=render
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