Interferon-γ-dependent inhibition of B cell activation by bone marrow-derived mesenchymal stem cells in a murine model of systemic lupus erythematosus

Francesca Schena, Claudio Gambini, Andrea Gregorio, Manuela Mosconi, Daniele Reverberi, Marco Gattorno, Simona Casazza, Antonio Uccelli, Lorenzo Moretta, Alberto Martini, Elisabetta Traggiai

Research output: Contribution to journalArticle

Abstract

Objective. Bone marrow - derived mesenchymal stem cells (BM-MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of immune-mediated diseases. This study was undertaken to assess the influence of murine BM-MSCs on the activation of B cells in (NZB x NZW)F1 mice as an animal model of systemic lupus erythematosus (SLE). Methods. We evaluated the in vitro effects of BM-MSCs on the proliferation and differentiation to plasma cells of splenic mature B cell subsets, namely follicular and marginal zone B cells isolated from (NZB x NZW)F1 mice. Lupus mice were also treated with BM-MSCs, and serum autoantibodies, proteinuria, histologic changes in the kidney, and survival rates were monitored. Results. BM-MSCs inhibited antigen-dependent proliferation and differentiation to plasma cells of follicular and marginal zone B cells in vitro. This inhibitory effect was dependent on interferon-γ (IFNγ) and was mediated by cell-to-cell contact, involving the programmed death 1 (PD-1)/PD ligand pathway. In vivo treatment with BM-MSCs did not affect the levels of anti-double-stranded DNA antibodies or proteinuria. However, a reduction in glomerular immune complex deposition, lymphocytic infiltration, and glomerular proliferation was observed. Conclusion. Our findings indicate that BM-MSCs affect B cell receptor - dependent activation of both follicular and marginal zone B cells from lupus mice. This inhibitory effect is IFNγ-dependent and cell contact - dependent. MSCs in vivo do not affect the production of autoantibodies, the level of proteinuria, or the mortality rates. Nonetheless, the significant improvement in histologic findings in the kidney supports the potential role of MSCs in the prevention of glomerular damage.

Original languageEnglish
Pages (from-to)2776-2786
Number of pages11
JournalArthritis and Rheumatism
Volume62
Issue number9
DOIs
Publication statusPublished - 2010

Fingerprint

Mesenchymal Stromal Cells
Systemic Lupus Erythematosus
Interferons
B-Lymphocytes
Bone Marrow
Proteinuria
Plasma Cells
Autoantibodies
B-Lymphocyte Subsets
Kidney
Immune System Diseases
Antigen-Antibody Complex
Cell Differentiation
Survival Rate
Animal Models
Cell Proliferation
Ligands
Antigens
Mortality
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Interferon-γ-dependent inhibition of B cell activation by bone marrow-derived mesenchymal stem cells in a murine model of systemic lupus erythematosus. / Schena, Francesca; Gambini, Claudio; Gregorio, Andrea; Mosconi, Manuela; Reverberi, Daniele; Gattorno, Marco; Casazza, Simona; Uccelli, Antonio; Moretta, Lorenzo; Martini, Alberto; Traggiai, Elisabetta.

In: Arthritis and Rheumatism, Vol. 62, No. 9, 2010, p. 2776-2786.

Research output: Contribution to journalArticle

Schena, Francesca ; Gambini, Claudio ; Gregorio, Andrea ; Mosconi, Manuela ; Reverberi, Daniele ; Gattorno, Marco ; Casazza, Simona ; Uccelli, Antonio ; Moretta, Lorenzo ; Martini, Alberto ; Traggiai, Elisabetta. / Interferon-γ-dependent inhibition of B cell activation by bone marrow-derived mesenchymal stem cells in a murine model of systemic lupus erythematosus. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 9. pp. 2776-2786.
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AU - Gregorio, Andrea

AU - Mosconi, Manuela

AU - Reverberi, Daniele

AU - Gattorno, Marco

AU - Casazza, Simona

AU - Uccelli, Antonio

AU - Moretta, Lorenzo

AU - Martini, Alberto

AU - Traggiai, Elisabetta

PY - 2010

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