Antigen-driven PD1+Tox+Eomes+ and PD1+Tox+BHLHE40+ synovial T lymphocytes regulate chronic inflammation in situ

Maschmeyer, P.; Heinz, G. A.; Skopnik, C.; 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.; Annunziato, F.; van Wijk, F.; Radbruch, A.; Kallinich, T.; Mashreghi, M.-F.

doi:10.1101/2019.12.27.884098

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bioRxiv · 10.1101/2019.12.27.884098

Antigen-driven PD1+Tox+Eomes+ and PD1+Tox+BHLHE40+ synovial T lymphocytes regulate chronic inflammation in situ

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Abstract

Introduction/AbstractT lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro-inflammatory cytokines upon re-stimulation in vitro1-29. 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)30-33. However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the heterogeneity of synovial T lymphocytes in JIA patients by single cell RNA-sequencing. We identify 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. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.

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Maschmeyer, P., Heinz, G. A., Skopnik, C., 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., Annunziato, F., van Wijk, F., Radbruch, A., Kallinich, T., Mashreghi, M.-F.. 2019-12-28. Antigen-driven PD1+Tox+Eomes+ and PD1+Tox+BHLHE40+ synovial T lymphocytes regulate chronic inflammation in situ. https://doi.org/10.1101/2019.12.27.884098

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