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Mesenchymal stem cell therapy induces FLT3L and CD1c+ dendritic cells in systemic lupus erythematosus patients

Author

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  • Xinran Yuan

    (The Affiliated Drum Tower Hospital of Nanjing University Medical School
    Nanjing University)

  • Xiaodong Qin

    (The Affiliated Drum Tower Hospital of Nanjing University Medical School)

  • Dandan Wang

    (The Affiliated Drum Tower Hospital of Nanjing University Medical School)

  • Zhuoya Zhang

    (The Affiliated Drum Tower Hospital of Nanjing University Medical School)

  • Xiaojun Tang

    (The Affiliated Drum Tower Hospital of Nanjing University Medical School)

  • Xiang Gao

    (Nanjing University)

  • Wanjun Chen

    (Mucosal Immunology Section, NIDCR, NIH)

  • Lingyun Sun

    (The Affiliated Drum Tower Hospital of Nanjing University Medical School
    Nanjing University)

Abstract

Allogeneic mesenchymal stem cells (MSCs) exhibit immunoregulatory function in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain incompletely understood. Here we show that the number of peripheral tolerogenic CD1c+ dendritic cells (DCs) and the levels of serum FLT3L are significantly decreased in SLE patients especially with lupus nephritis, compared to healthy controls. Transplantation of allogeneic umbilical cord-derived MSCs (UC-MSCs) significantly up-regulates peripheral blood CD1c+DCs and serum FLT3L. Mechanistically, UC-MSCs express FLT3L that binds to FLT3 on CD1c+DCs to promote the proliferation and inhibit the apoptosis of tolerogenic CD1c+DCs. Conversely, reduction of FLT3L with small interfering RNA in MSCs abolishes the up-regulation of tolerogenic CD1c+DCs in lupus patients treated with MSCs. Interferon-γ induces FLT3L expression in UC-MSCs through JAK/STAT signaling pathway. Thus, allogeneic MSCs might suppress inflammation in lupus through up-regulating tolerogenic DCs.

Suggested Citation

  • Xinran Yuan & Xiaodong Qin & Dandan Wang & Zhuoya Zhang & Xiaojun Tang & Xiang Gao & Wanjun Chen & Lingyun Sun, 2019. "Mesenchymal stem cell therapy induces FLT3L and CD1c+ dendritic cells in systemic lupus erythematosus patients," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10491-8
    DOI: 10.1038/s41467-019-10491-8
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