Mesenchymal Stem Cell Therapy Induces FLT3L and CD1c+ Dendritic Cells in Systemic Lupus Erythematosus Patients

Xinran Yuan ¹, Dandan Wang ¹ and Lingyun Sun², ¹Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China (People's Republic), ²The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China (People's Republic)

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: dendritic cells and FLT3L, MSCs, SLE

Session Information

Date: Sunday, November 10, 2019

Session Title: 3S081: SLE – Clinical I: Clinical Trials (857–862)

Session Type: ACR Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: 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.

Methods: Totally, 166 SLE patients and 78 healthy subjects were included in this study. Tolerogenic DCs were isolated as Lin(CD3/19/56/14)^– HLA DR⁺CD11c⁺CD1c⁺ from peripheral blood mononuclear cells (PBMCs). Level of tolerogenic DCs was determined by flow cytometry, and serum concentration of FLT3L was assessed by ELISA from healthy controls and SLE patients. Twenty-one SLE patients were given MSCs infusions. We compared the number and function of tolerogenic DCs, as well as serum FLT3L before and after MSCs transplantation. PBMCs from SLE patients were collected and co-cultured with MSCs, to detect the number and function of tolerogenic DCs. The level of FLT3L in the supernatant solution was analyzed. FLT3L siRNA was added to the co-culture system, and the level of tolerogenic DCs was detected.

Results: 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.

Conclusion: In summary, allogeneic MSCs might suppress inflammation in lupus through up-regulating tolerogenic DCs.

Graphical Abstract

Disclosure: X. Yuan, None; D. Wang, None; L. Sun, None.

To cite this abstract in AMA style:

Yuan X, Wang D, Sun L. Mesenchymal Stem Cell Therapy Induces FLT3L and CD1c+ Dendritic Cells in Systemic Lupus Erythematosus Patients [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/mesenchymal-stem-cell-therapy-induces-flt3l-and-cd1c-dendritic-cells-in-systemic-lupus-erythematosus-patients/. Accessed February 18, 2020.

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