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Antigen‐driven PD‐1 + TOX + BHLHE40 + and PD‐1 + TOX + EOMES + T lymphocytes regulate juvenile idiopathic arthritis in situ
Author(s) -
Maschmeyer Patrick,
Heinz Gitta Anne,
Skopnik Christopher Mark,
Lutter Lisanne,
Mazzoni Alessio,
Heinrich Frederik,
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 HyunDong,
Durek Pawel,
Annunziato Francesco,
Wijk Femke,
Radbruch Andreas,
Kallinich Tilmann,
Mashreghi MirFarzin
Publication year - 2021
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.202048797
Subject(s) - biology , population , antigen , microbiology and biotechnology , immunology , immune system , cd8 , t cell receptor , t lymphocyte , t cell , tcirg1 , arthritis , cytotoxic t cell , genetics , in vitro , medicine , environmental health
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.