
Mesenchymal Stromal Cells Induce Peculiar Alternatively Activated Macrophages Capable of Dampening Both Innate and Adaptive Immune Responses
Author(s) -
Chiossone Laura,
Conte Romana,
Spaggiari Grazia Maria,
Serra Martina,
Romei Cristina,
Bellora Francesca,
Becchetti Flavio,
Andaloro Antonio,
Moretta Lorenzo,
Bottino Cristina
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2369
Subject(s) - biology , mesenchymal stem cell , microbiology and biotechnology , innate immune system , proinflammatory cytokine , immune system , haematopoiesis , stromal cell , acquired immune system , immunology , inflammation , cancer research , stem cell
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 (M MSC ), through a prostaglandin E2‐dependent mechanism. M MSC 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 M MSC , which differed from those of typical IL‐4‐induced macrophages (M2). In particular, interacting with activated natural killer (NK) cells, M MSC 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, M MSC 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 M MSC 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. S tem C ells 2016;34:1909–1921