Signaling Through gp130 Compromises Suppressive Function in Human FOXP3+ Regulatory T Cells

Frontiers in Immunology
Khalid Bin DhubanC A Piccirillo

Abstract

The CD4+FOXP3+ regulatory T cell (Treg) subset is an indispensable mediator of immune tolerance. While high and stable expression of the transcription factor FOXP3 is considered a hallmark feature of Treg cells, our previous studies have demonstrated that the human FOXP3+ subset is functionally heterogeneous, whereby a sizeable proportion of FOXP3+ cells in healthy individuals have a diminished capacity to suppress the proliferation and cytokine production of responder cells. Notably, these non-suppressive cells are indistinguishable from suppressive Treg cells using conventional markers of human Treg. Here we investigate potential factors that underlie loss of suppressive function in human Treg cells. We show that high expression of the IL-6 family cytokine receptor subunit gp130 identifies Treg cells with reduced suppressive capacity ex vivo and in primary FOXP3+ clones. We further show that two gp130-signaling cytokines, IL-6 and IL-27, impair the suppressive capacity of human Treg cells. Finally, we show that gp130 signaling reduces the expression of the transcription factor Helios, whose expression is essential for stable Treg function. These results highlight the role of gp130 in regulating human Treg function, and sugges...Continue Reading

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Citations

Aug 17, 2020·Scandinavian Journal of Immunology·Abdollah JafarzadehBhaskar Saha
Nov 5, 2019·Frontiers in Oncology·Olena KourkoKatrina Gee
Apr 3, 2020·Chinese Journal of Integrative Medicine·Yu-Guo WangYong-Qi Dou
Jun 22, 2021·Frontiers in Immunology·Nur Diyana Mohd ShukriKah Keng Wong
Aug 20, 2021·Frontiers in Immunology·Lauren Van ZeebroeckMarkus Kleinewietfeld
Aug 27, 2021·Molecular Immunology·Youwen MeiHongbo Qi

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Methods Mentioned

BETA
FACS
flow cytometry

Software Mentioned

GraphPad Prism

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