Human Bone Marrow-Derived Mesenchymal Stromal Cells Differentially Inhibit Cytokine Production by Peripheral Blood Monocytes Subpopulations and Myeloid Dendritic Cells.

Paula Laranjeira,Artur Paiva,Joana Gomes,Rosario Domingues,Susana Pedreiro,Tania Ribeiro,Francisco Santos,Manuel Abecasis,Antonio Martinho,Monia Pedrosa,Helder Trindade,Brigida Antunes

doi:10.1155/2015/819084

Abstract

The immunosuppressive properties of mesenchymal stromal/stem cells (MSC) rendered them an attractive therapeutic approach for immune disorders and an increasing body of evidence demonstrated their clinical value. However, the influence of MSC on the function of specific immune cell populations, namely, monocyte subpopulations, is not well elucidated. Here, we investigated the influence of human bone marrow MSC on the cytokine and chemokine expression by peripheral blood classical, intermediate and nonclassical monocytes, and myeloid dendritic cells (mDC), stimulated with lipopolysaccharide plus interferon (IFN)γ. We found that MSC effectively inhibit tumor necrosis factor- (TNF-) α and macrophage inflammatory protein- (MIP-) 1β protein expression in monocytes and mDC, without suppressing CCR7 and CD83 protein expression. Interestingly, mDC exhibited the highest degree of inhibition, for both TNF-α and MIP-1β, whereas the reduction of TNF-α expression was less marked for nonclassical monocytes. Similarly, MSC decreased mRNA levels of interleukin- (IL-) 1β and IL-6 in classical monocytes, CCL3, CCL5, CXCL9, and CXCL10 in classical and nonclassical monocytes, and IL-1β and CXCL10 in mDC. MSC do not impair the expression of maturation markers in monocytes and mDC under our experimental conditions; nevertheless, they hamper the proinflammatory function of monocytes and mDC, which may impede the development of inflammatory immune responses.

Highlights

Mesenchymal stromal/stem cells (MSC) correspond to undifferentiated cells capable of self-renewal and to differentiate along different cell lineages [1]
In order to better understand how MSC regulate the immune function of the recently described monocyte subpopulations and myeloid dendritic cells (mDC), we evaluated the expression of proteins involved in cell migration, activation/maturation, antigen presentation, and the production of proinflammatory cytokines, in LPS
Considering tumor necrosis factor- (TNF-)α and macrophage inflammatory protein- (MIP-)1β expression, our results showed that MSC decreased both the percentage of cells producing TNF-α and MIP-1β (P < 0.05, for all cell populations) as well as the amount of protein produced per cell, wherein MSC depletion prior to LPS + IFNγ stimulation resulted in a less effective reduction of the percentage of TNF-α producing monocytes (Figure 2(a))

Summary

Introduction

Mesenchymal stromal/stem cells (MSC) correspond to undifferentiated cells capable of self-renewal and to differentiate along different cell lineages [1]. An increasing number of studies have reported the inhibitory effect of MSC over immune cells, wherein the majority of them focused on T lymphocytes [5, 6]. Even concerning T cells, only a limited number of studies analyzed and compared the influence of MSC. As antigen-presenting cells have a pivotal role in T cell activation, in T cell differentiation, and in directing their polarization [12], the study of MSC influence over monocytes and dendritic cells (DC) became an active field of research. To the best of our knowledge, no study investigated and compared the influence of MSC over the recently identified peripheral blood classical, intermediate, and nonclassical monocyte subpopulations [15]

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