Toll-Like Receptors 3 and 4 Are Expressed by Human Bone Marrow-Derived Mesenchymal Stem Cells and Can Inhibit Their T-Cell Modulatory Activity by Impairing Notch Signaling

Liotta, Francesco; Angeli, Roberta; Cosmi, Lorenzo; Filì, Lucia; Manuelli, Cinzia; Frosali, Francesca; Mazzinghi, Benedetta; Maggi, Laura; Pasini, Anna Fratta; Lisi, Veronica; Santarlasci, Veronica; Consoloni, Lara; Angelotti, Maria Lucia; Romagnani, Paola; Parronchi, Paola; Krampera, Mauro; Maggi, Enrico; Romagnani, Sergio; Annunziato, Francesco

doi:10.1634/stemcells.2007-0454

Cited by 446 publications

(457 citation statements)

References 69 publications

Supporting

Mentioning

409

Contrasting

Unclassified

Order By: Relevance

“…54 Moreover, engagement of TLR-4 on MSC by lipopolysaccharide has been shown to result in the generation of pro-inflammatory MSC 55 and to suppress their immunosuppressive activity, 56 although this is still a matter of debate. 57 Whether HMGB1 induces a similar phenotype in MSC is currently being determined.…”

Section: Migration Of Msc Towards Recombinant Hgf Was Inhibitedmentioning

confidence: 99%

Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death

et al. 2015

View full text Add to dashboard Cite

Tissue damage due to apoptotic or necrotic cell death typically initiates distinct cellular responses, leading either directly to tissue repair and regeneration or to immunological processes first, to clear the site, for example, of potentially damage-inducing agents. Mesenchymal stem cells (MSC) as well as immature dendritic cells (iDC) and monocytes migrate to injured tissues. MSC have regenerative capacity, whereas monocytes and iDC have a critical role in inflammation and induction of immune responses, including autoimmunity after tissue damage. Here, we investigated the influence of apoptotic and necrotic cell death on recruitment of MSC, monocytes and iDC, and identified hepatocyte growth factor (HGF) and the alarmin high mobility group box 1 (HMGB1) as key factors differentially regulating these migratory responses. MSC, but not monocytes or iDC, were attracted by apoptotic cardiomyocytic and neuronal cells, whereas necrosis induced migration of monocytes and iDC, but not of MSC. Only apoptotic cell death resulted in HGF production and HGF-mediated migration of MSC towards the apoptotic targets. In contrast, HMGB1 was predominantly released by the necrotic cells and mediated recruitment of monocytes and iDC via the receptor of advanced glycation end products. Moreover, necrotic cardiomyocytic and neuronal cells caused an HMGB1/toll-like receptor-4-dependent inhibition of MSC migration towards apoptosis or HGF, while recruitment of monocytes and iDC by necrosis or HMGB1 was not affected by apoptotic cells or HGF. Thus, the type of cell death differentially regulates recruitment of either MSC or monocytes and iDC through HGF and HMGB1, respectively, with a dominant, HMGB1-mediated role of necrosis in determining tropism after tissue injury.

show abstract

Section: Migration Of Msc Towards Recombinant Hgf Was Inhibitedmentioning

confidence: 99%

Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Activation of human MSCs by TLR ligands induces IL-6, IL-8 and CXCL10 secretion and NF-kB nuclear translocation in vitro (Liotta et al, 2008). TLR 3 and 4 ligation via lipopolysaccharide (LPS) reduces the suppressive activity of MSCs on proliferating T cells (Tomchuck et al, 2008), while increasing their reprogramming capacity on macrophages by a prostaglandin (PG) E2-dependent mechanism (Nemeth et al, 2009).…”

Section: Modulation Of Immune Responsesmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

View full text Add to dashboard Cite

Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

show abstract

“…Recently, several reports showed that engagement of different Toll-like receptors (TLRs) in MSCs either enhanced or inhibited their immunosuppressive properties [11][12][13]. mostly immunosuppressive ones [12].…”

Section: Introductionmentioning

confidence: 99%

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

et al. 2012

View full text Add to dashboard Cite

Toll-Like Receptors 3 and 4 Are Expressed by Human Bone Marrow-Derived Mesenchymal Stem Cells and Can Inhibit Their T-Cell Modulatory Activity by Impairing Notch Signaling

Abstract: STEM CELLS 2008;26:279 -289 Disclosure of potential conflicts of interest is found at the end of this article.

Cited by 446 publications

References 69 publications

Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death

Necrotic cell-derived high mobility group box 1 attracts antigen-presenting cells but inhibits hepatocyte growth factor-mediated tropism of mesenchymal stem cells for apoptotic cell death

How stem cells speak with host immune cells in inflammatory brain diseases

A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

Contact Info

Product

Resources

About