Laboratory of Clinical and Experimental Immunology

Laboratory of, Italy

Laboratory of Clinical and Experimental Immunology

Laboratory of, Italy

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Chiossone L.,Laboratory of Clinical and Experimental Immunology | Conte R.,Laboratory of Immunology | Serra M.,Laboratory of Clinical and Experimental Immunology | Romei C.,Laboratory of Clinical and Experimental Immunology | And 3 more authors.
Stem Cells | Year: 2016

Mesenchymal stromal cells (MSCs) support hematopoiesis and exert immunoregulatory activities. Here, we analyzed the functional outcome of the interactions between MSCs and monocytes/macrophages. We showed that MSCs supported the survival of monocytes that underwent differentiation into macrophages, in the presence of macrophage colony-stimulating factor. However, MSCs skewed their polarization toward a peculiar M2-like functional phenotype (MMSC), through a prostaglandin E2-dependent mechanism. MMSC were characterized by high expression of scavenger receptors, increased phagocytic capacity, and high production of interleukin (IL)-10 and transforming growth factor-β. These cytokines contributed to the immunoregulatory properties of MMSC, which differed from those of typical IL-4-induced macrophages (M2). In particular, interacting with activated natural killer (NK) cells, MMSC inhibited both the expression of activating molecules such as NKp44, CD69, and CD25 and the production of IFNγ, while M2 affected only IFNγ production. Moreover, MMSC inhibited the proliferation of CD8+ T cells in response to allogeneic stimuli and induced the expansion of regulatory T cells (Tregs). Toll-like receptor engagement reverted the phenotypic and functional features of MMSC to those of M1 immunostimulatory/proinflammatory macrophages. Overall our data show that MSCs induce the generation of a novel type of alternatively activated macrophages capable of suppressing both innate and adaptive immune responses. These findings may help to better understand the role of MSCs in healthy tissues and inflammatory diseases including cancer, and provide clues for novel therapeutic approaches. Stem Cells 2016 © 2016 AlphaMed Press.


Morandi F.,G Gaslini Institute | Ferretti E.,G Gaslini Institute | Castriconi R.,University of Genoa | Dondero A.,University of Genoa | And 4 more authors.
Blood | Year: 2011

Soluble HLA-G (sHLA-G) inhibits natural killer (NK) cell functions. Here, we investigated sHLA-G-mediated modulation of (1) chemokine receptor and NK receptor expression and function and (2) cytokine and chemokine secretion in CD56 bright and CD56 dim NK cells. sHLA-Gtreated or untreated peripheral blood (PB) and tonsil NK cells were analyzed for chemokine receptor and NK receptor expression by flow cytometry. sHLA-G down-modulated (1) CXCR3 on PB and tonsil CD56 bright and CD56 dim, (2) CCR2 on PB and tonsil CD56 bright, (3) CX 3CR1 on PB CD56 dim, (4) CXCR5 on tonsil CD56 dim, and (5) CD94/NKG2A on PB and tonsil CD56 bright and CD56 dimNK cells. Such sHLA-G-mediated downmodulations were reverted by adding anti-HLA-G or anti-ILT2 mAbs. sHLA-G inhibited chemotaxis of (1) PB NK cells toward CXCL10, CXCL11, and CX 3CL1 and (2) PB CD56 bright NK cells toward CCL2 and CXCL10. IFN-γ secretion induced by NKp46 engagement was inhibited by NKG2A engagement in untreated but not in sHLA-G-treated NK cells. sHLA-G up-regulated secretion of (1) CCL22 in CD56 bright and CD56 dim and (2) CCL2, CCL8, and CXCL2-CXCL3 in CD56 dim PB NK cells. Signal transduction experiments showed sHLA-G-mediated down-modulation of Stat5 phosphorylation in PB NK cells. In conclusion, our data delineated novel mechanisms of sHLA-G-mediated inhibition of NK-cell functions. © 2011 by The American Society of Hematology.

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