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Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ

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Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ. / Maschmeyer, Patrick; Heinz, Gitta Anne; Skopnik, Christopher Mark; Lutter, Lisanne; Mazzoni, Alessio; Heinrich, Frederik; von Stuckrad, Sae Lim; Wirth, Lorenz Elias; Tran, Cam Loan; Riedel, René; Lehmann, Katrin; Sakwa, Imme; Cimaz, Rolando; Giudici, Francesco; Mall, Marcus Alexander; Enghard, Philipp; Vastert, Bas; Chang, Hyun-Dong; Durek, Pawel; Annunziato, Francesco; van Wijk, Femke; Radbruch, Andreas; Kallinich, Tilmann; Mashreghi, Mir-Farzin.

In: EUR J IMMUNOL, Vol. 51, No. 4, 04.2021, p. 915-929.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Maschmeyer, P, Heinz, GA, Skopnik, CM, Lutter, L, Mazzoni, A, Heinrich, F, von Stuckrad, SL, Wirth, LE, Tran, CL, Riedel, R, Lehmann, K, Sakwa, I, Cimaz, R, Giudici, F, Mall, MA, Enghard, P, Vastert, B, Chang, H-D, Durek, P, Annunziato, F, van Wijk, F, Radbruch, A, Kallinich, T & Mashreghi, M-F 2021, 'Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ', EUR J IMMUNOL, vol. 51, no. 4, pp. 915-929. https://doi.org/10.1002/eji.202048797

APA

Maschmeyer, P., Heinz, G. A., Skopnik, C. M., Lutter, L., Mazzoni, A., Heinrich, F., von Stuckrad, S. L., Wirth, L. E., Tran, C. L., Riedel, R., Lehmann, K., Sakwa, I., Cimaz, R., Giudici, F., Mall, M. A., Enghard, P., Vastert, B., Chang, H-D., Durek, P., ... Mashreghi, M-F. (2021). Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ. EUR J IMMUNOL, 51(4), 915-929. https://doi.org/10.1002/eji.202048797

Vancouver

Maschmeyer P, Heinz GA, Skopnik CM, Lutter L, Mazzoni A, Heinrich F et al. Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ. EUR J IMMUNOL. 2021 Apr;51(4):915-929. https://doi.org/10.1002/eji.202048797

Bibtex

@article{70997b47094d416fb6133d12069ccce5,
title = "Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ",
abstract = "T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single-cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1+ TOX+ EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+ TOX+ BHLHE40+ population of CD4+ , and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation in situ. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.",
keywords = "Antigens/immunology, Arthritis, Juvenile/genetics, Basic Helix-Loop-Helix Transcription Factors/immunology, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, Cells, Cultured, Gene Expression Profiling/methods, High Mobility Group Proteins/immunology, Homeodomain Proteins/immunology, Humans, Programmed Cell Death 1 Receptor/immunology, RNA-Seq/methods, Receptors, Antigen, T-Cell/genetics, Single-Cell Analysis/methods, T-Box Domain Proteins/immunology, T-Lymphocytes/immunology, Transcriptome/genetics",
author = "Patrick Maschmeyer and Heinz, {Gitta Anne} and Skopnik, {Christopher Mark} and Lisanne Lutter and Alessio Mazzoni and Frederik Heinrich and {von Stuckrad}, {Sae Lim} and Wirth, {Lorenz Elias} and Tran, {Cam Loan} and Ren{\'e} Riedel and Katrin Lehmann and Imme Sakwa and Rolando Cimaz and Francesco Giudici and Mall, {Marcus Alexander} and Philipp Enghard and Bas Vastert and Hyun-Dong Chang and Pawel Durek and Francesco Annunziato and {van Wijk}, Femke and Andreas Radbruch and Tilmann Kallinich and Mir-Farzin Mashreghi",
note = "{\textcopyright} 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.",
year = "2021",
month = apr,
doi = "10.1002/eji.202048797",
language = "English",
volume = "51",
pages = "915--929",
journal = "EUR J IMMUNOL",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag GmbH",
number = "4",

}

RIS

TY - JOUR

T1 - Antigen-driven PD-1+ TOX+ BHLHE40+ and PD-1+ TOX+ EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ

AU - Maschmeyer, Patrick

AU - Heinz, Gitta Anne

AU - Skopnik, Christopher Mark

AU - Lutter, Lisanne

AU - Mazzoni, Alessio

AU - Heinrich, Frederik

AU - von Stuckrad, Sae Lim

AU - Wirth, Lorenz Elias

AU - Tran, Cam Loan

AU - Riedel, René

AU - Lehmann, Katrin

AU - Sakwa, Imme

AU - Cimaz, Rolando

AU - Giudici, Francesco

AU - Mall, Marcus Alexander

AU - Enghard, Philipp

AU - Vastert, Bas

AU - Chang, Hyun-Dong

AU - Durek, Pawel

AU - Annunziato, Francesco

AU - van Wijk, Femke

AU - Radbruch, Andreas

AU - Kallinich, Tilmann

AU - Mashreghi, Mir-Farzin

N1 - © 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

PY - 2021/4

Y1 - 2021/4

N2 - T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single-cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1+ TOX+ EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+ TOX+ BHLHE40+ population of CD4+ , and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation in situ. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.

AB - T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single-cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD-1+ TOX+ EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD-1+ TOX+ BHLHE40+ population of CD4+ , and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation in situ. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.

KW - Antigens/immunology

KW - Arthritis, Juvenile/genetics

KW - Basic Helix-Loop-Helix Transcription Factors/immunology

KW - CD4-Positive T-Lymphocytes/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - Cells, Cultured

KW - Gene Expression Profiling/methods

KW - High Mobility Group Proteins/immunology

KW - Homeodomain Proteins/immunology

KW - Humans

KW - Programmed Cell Death 1 Receptor/immunology

KW - RNA-Seq/methods

KW - Receptors, Antigen, T-Cell/genetics

KW - Single-Cell Analysis/methods

KW - T-Box Domain Proteins/immunology

KW - T-Lymphocytes/immunology

KW - Transcriptome/genetics

U2 - 10.1002/eji.202048797

DO - 10.1002/eji.202048797

M3 - SCORING: Journal article

C2 - 33296081

VL - 51

SP - 915

EP - 929

JO - EUR J IMMUNOL

JF - EUR J IMMUNOL

SN - 0014-2980

IS - 4

ER -