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

著者: Patrick Maschmeyer, Gitta Anne Heinz, Christopher Mark Skopnik, Lisanne Lutter, Alessio Mazzoni, Frederik Heinrich, Anne Sae Lim von Stuckrad, Lorenz Wirth, Cam Loan Tran, René Riedel, Katrin Lehmann, Imme Sakwa, Rolando Cimaz, Francesco Giudici, Marcus Mall, Philipp Enghard, Sebastiaan J. Vastert, Hyun‐Dong Chang, Pawel Durek, Francesco Annunziato, Femke van Wijk, Andreas Radbruch, Tilmann Kallinich, Mir‐Farzin Mashreghi - European Journal of Immunology 2020 被引用: 41

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.