Systemic lupus erythematosus favors the generation of IL-17 producing double negative T cells

Hao Li, Iannis E. Adamopoulos, Vaishali R. Moulton, Isaac E. Stillman, Zach Herbert, James J. Moon, Amir Sharabi, Suzanne Krishfield, Maria G. Tsokos, George C. Tsokos

    Research output: Contribution to journalArticle

    Abstract

    Mature double negative (DN) T cells are a population of αβ T cells that lack CD4 and CD8 coreceptors and contribute to systemic lupus erythematosus (SLE). The splenic marginal zone macrophages (MZMs) are important for establishing immune tolerance, and loss of their number or function contributes to the progression of SLE. Here we show that loss of MZMs impairs the tolerogenic clearance of apoptotic cells and alters the serum cytokine profile, which in turn provokes the generation of DN T cells from self-reactive CD8+ T cells. Increased Ki67 expression, narrowed TCR V-beta repertoire usage and diluted T-cell receptor excision circles confirm that DN T cells from lupus-prone mice and patients with SLE undergo clonal proliferation and expansion in a self-antigen dependent manner, which supports the shared mechanisms for their generation. Collectively, our results provide a link between the loss of MZMs and the expansion of DN T cells, and indicate possible strategies to prevent the development of SLE.

    Original languageEnglish (US)
    Article number2859
    JournalNature communications
    Volume11
    Issue number1
    DOIs
    StatePublished - Dec 1 2020

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

    Fingerprint Dive into the research topics of 'Systemic lupus erythematosus favors the generation of IL-17 producing double negative T cells'. Together they form a unique fingerprint.

  • Cite this

    Li, H., Adamopoulos, I. E., Moulton, V. R., Stillman, I. E., Herbert, Z., Moon, J. J., Sharabi, A., Krishfield, S., Tsokos, M. G., & Tsokos, G. C. (2020). Systemic lupus erythematosus favors the generation of IL-17 producing double negative T cells. Nature communications, 11(1), [2859]. https://doi.org/10.1038/s41467-020-16636-4