Autor: |
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, Hyun‐Dong, Durek, Pawel, Annunziato, Francesco |
Předmět: |
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Zdroj: |
European Journal of Immunology; Apr2021, Vol. 51 Issue 4, p915-929, 15p |
Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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