Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation

Gerdien Mijnheer; Lisanne Lutter; Michal Mokry; Marlot van der Wal; Rianne Scholman; Veerle Fleskens; Aridaman Pandit; Weiyang Tao; Mark Wekking; Stephin Vervoort; Ceri Roberts; Alessandra Petrelli; Janneke G.C. Peeters; Marthe Knijff; Sytze de Roock; Sebastiaan Vastert; Leonie S. Taams; Jorg van Loosdregt; Femke van Wijk

doi:10.1038/s41467-021-22975-7

Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation

Gerdien Mijnheer, Lisanne Lutter, Michal Mokry, Marlot van der Wal, Rianne Scholman, Veerle Fleskens, Aridaman Pandit, Weiyang Tao, Mark Wekking, Stephin Vervoort, Ceri Roberts, Alessandra Petrelli, Janneke G.C. Peeters, Marthe Knijff, Sytze de Roock, Sebastiaan Vastert, Leonie S. Taams, Jorg van Loosdregt, Femke van Wijk

Inflammation Biology

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

Abstract

Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations.

Original language	English
Article number	2710
Pages (from-to)	2710
Number of pages	1
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-22975-7
Publication status	Published - Dec 2021

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Mijnheer, G., Lutter, L., Mokry, M., van der Wal, M., Scholman, R., Fleskens, V., Pandit, A., Tao, W., Wekking, M., Vervoort, S., Roberts, C., Petrelli, A., Peeters, J. G. C., Knijff, M., de Roock, S., Vastert, S., Taams, L. S., van Loosdregt, J., & van Wijk, F. (2021). Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation. Nature Communications, 12(1), 2710. Article 2710. https://doi.org/10.1038/s41467-021-22975-7

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title = "Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation",

abstract = "Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations.",

author = "Gerdien Mijnheer and Lisanne Lutter and Michal Mokry and {van der Wal}, Marlot and Rianne Scholman and Veerle Fleskens and Aridaman Pandit and Weiyang Tao and Mark Wekking and Stephin Vervoort and Ceri Roberts and Alessandra Petrelli and Peeters, {Janneke G.C.} and Marthe Knijff and {de Roock}, Sytze and Sebastiaan Vastert and Taams, {Leonie S.} and {van Loosdregt}, Jorg and {van Wijk}, Femke",

note = "Funding Information: We would like to thank J. van Velzen and P. Andriessen van der Burght for technical assistance, and Anoushka Samat for help with qPCR primer design. F. van Wijk is supported by a VIDI grant from ZonMw (91714332). Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = dec,

doi = "10.1038/s41467-021-22975-7",

language = "English",

volume = "12",

pages = "2710",

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Mijnheer, G, Lutter, L, Mokry, M, van der Wal, M, Scholman, R, Fleskens, V, Pandit, A, Tao, W, Wekking, M, Vervoort, S, Roberts, C, Petrelli, A, Peeters, JGC, Knijff, M, de Roock, S, Vastert, S, Taams, LS, van Loosdregt, J & van Wijk, F 2021, 'Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation', Nature Communications, vol. 12, no. 1, 2710, pp. 2710. https://doi.org/10.1038/s41467-021-22975-7

TY - JOUR

T1 - Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation

AU - Mijnheer, Gerdien

AU - Lutter, Lisanne

AU - Mokry, Michal

AU - van der Wal, Marlot

AU - Scholman, Rianne

AU - Fleskens, Veerle

AU - Pandit, Aridaman

AU - Tao, Weiyang

AU - Wekking, Mark

AU - Vervoort, Stephin

AU - Roberts, Ceri

AU - Petrelli, Alessandra

AU - Peeters, Janneke G.C.

AU - Knijff, Marthe

AU - de Roock, Sytze

AU - Vastert, Sebastiaan

AU - Taams, Leonie S.

AU - van Loosdregt, Jorg

AU - van Wijk, Femke

N1 - Funding Information: We would like to thank J. van Velzen and P. Andriessen van der Burght for technical assistance, and Anoushka Samat for help with qPCR primer design. F. van Wijk is supported by a VIDI grant from ZonMw (91714332). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/12

Y1 - 2021/12

N2 - Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations.

AB - Treg cells are critical regulators of immune homeostasis, and environment-driven Treg cell differentiation into effector (e)Treg cells is crucial for optimal functioning. However, human Treg cell programming in inflammation is unclear. Here, we combine transcriptional and epigenetic profiling to identify a human eTreg cell signature. Inflammation-derived functional Treg cells have a transcriptional profile characterized by upregulation of both a core Treg cell (FOXP3, CTLA4, TIGIT) and effector program (GITR, BLIMP-1, BATF). We identify a specific human eTreg cell signature that includes the vitamin D receptor (VDR) as a predicted regulator in eTreg cell differentiation. H3K27ac/H3K4me1 occupancy indicates an altered (super-)enhancer landscape, including enrichment of the VDR and BATF binding motifs. The Treg cell profile has striking overlap with tumor-infiltrating Treg cells. Our data demonstrate that human inflammation-derived Treg cells acquire a conserved and specific eTreg cell profile guided by epigenetic changes, and fine-tuned by environment-specific adaptations.

UR - http://www.scopus.com/inward/record.url?scp=85105769529&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-22975-7

DO - 10.1038/s41467-021-22975-7

M3 - Article

C2 - 33976194

AN - SCOPUS:85105769529

SN - 2041-1723

VL - 12

SP - 2710

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2710

ER -

Conserved human effector Treg cell transcriptomic and epigenetic signature in arthritic joint inflammation

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