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, Jahrgang 51, Nr. 4, 04.2021, S. 915-929.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -