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Journal of immunology (Baltimore, Md. : 1950)

Impaired B cell inhibition by lupus bone marrow mesenchymal stem cells is caused by reduced CCL2 expression.


PMID 25339674

Abstract

Mesenchymal stem cells (MSC) from healthy human and normal mice can inhibit normal B cell proliferation, differentiation, and Ab secretion in vitro. However, it remains unknown whether MSC from lupus-like mice and patients with systemic lupus erythematosus (SLE) exhibit the same immunoregulatory activity as normal MSC for B cell inhibition and, if not, what the underlying molecular mechanism would be. In this study, we showed that bone marrow-derived MSCs from lupus-like mice and SLE patients had an impairment in suppressing normal B cell proliferation and differentiation, which was caused by the reduction of CCL2 levels. Knockdown of CCL2 in normal MSC damaged their suppressive capacity for B cells. Conversely, overexpression of CCL2 in lupus MSCs restored their immunoregulatory ability for B cells in vitro and ameliorated the pathology of lupus nephritis and serological changes in MRL/lpr mice in vivo. Mechanistically, MSC-mediated B cell inhibition was dependent on matrix metalloproteinase proteolytic processing of CCL2. These findings reveal a novel function of CCL2 in B cell regulation by MSCs and suggest that CCL2 manipulation on MSCs may serve as a potential pathway for developing the more effective MSC-based therapy in autoimmune diseases associated with B cell activation, such as SLE.