Novel CD47: SIRPα Dependent Mechanism for the Activation of STAT3 in Antigen-Presenting Cell

Natan, Toledano; Gur‐Wahnon, Devorah; Adi, Ben-Yehuda; Rachmilewitz, Jacob

doi:10.1371/journal.pone.0075595

Cited by 19 publications

(16 citation statements)

References 43 publications

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“…This protein, which has thus far received little attention in the MSC literature, binds to the SIRPα receptor on macrophages and has been described as a “don’t eat me” signal (blocks phagocytosis) that may also promote peripheral tolerance. 34 This pathway has been implicated as a mechanism for tumor immune escape, and could be an interesting lead to pursue for MSC immunomodulation. 35…”

Section: Discussionmentioning

confidence: 99%

The influence of hypoxia and IFN-γ on the proteome and metabolome of therapeutic mesenchymal stem cells

et al. 2018

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Over the past 15 years, mesenchymal stem cells (MSCs) have been assessed for their capacity to suppress inflammation and promote tissue repair. Regardless of whether the cells are primed (exposed to instructive cues) before administration, their phenotype will respond to environmental signals present in the pathophysiological setting being treated. Since hypoxia and inflammation coexist in the settings of acute injury and chronic disease we sought to explore how the proteome and metabolome of MSCs changes when cells were exposed to 48 h of 1% oxygen, interferon gamma (IFN-γ), or both cues together. We specifically focused on changes in cell metabolism, immune modulation, extracellular matrix secretion and modification, and survival capacity. IFN-γ promoted expression of anti-pathogenic proteins and induced MSCs to limit inflammation and fibrosis while promoting their own survival. Hypoxia instead led to cell adaptation to low oxygen, including upregulation of proteins involved in anaerobic metabolism, autophagy, angiogenesis, and cell migration. While dual priming resulted in additive effects, we also found many instances of synergy. These data lend insight to how MSCs may behave after administration to a patient and suggest how priming cells beforehand could improve their therapeutic capacity.

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Section: Discussionmentioning

confidence: 99%

The influence of hypoxia and IFN-γ on the proteome and metabolome of therapeutic mesenchymal stem cells

et al. 2018

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“…Epithelial cells of the intestine express the surface protein CD47 which can directly interact with signal regulatory protein α (SIRP α ) expressed on the surface of DCs which underlie the intestinal epithelial cell layer. This protein-protein-interaction has been shown to result in a janus kinase-2 (JAK-2) dependent signal transducer and activator of transcription 3 (STAT3) activation downstream of SIRP α in DCs [ 79 ]. STAT3 activation, in turn, leads to enhanced IL-10 secretion from DCs and therefore promotes tolerogenic properties in the intestinal environment [ 79 ].…”

Section: Possible Molecular Mechanisms Of DC Tolerance Induction Imentioning

confidence: 99%

“…This protein-protein-interaction has been shown to result in a janus kinase-2 (JAK-2) dependent signal transducer and activator of transcription 3 (STAT3) activation downstream of SIRP α in DCs [ 79 ]. STAT3 activation, in turn, leads to enhanced IL-10 secretion from DCs and therefore promotes tolerogenic properties in the intestinal environment [ 79 ]. STAT3 has long been known as a crucial negative regulator of immunity.…”

Section: Possible Molecular Mechanisms Of DC Tolerance Induction Imentioning

confidence: 99%

Molecular Mechanisms of Induction of Tolerant and Tolerogenic Intestinal Dendritic Cells in Mice

Steimle

Frick

2016

Journal of Immunology Research

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How does the host manage to tolerate its own intestinal microbiota? A simple question leading to complicated answers. In order to maintain balanced immune responses in the intestine, the host immune system must tolerate commensal bacteria in the gut while it has to simultaneously keep the ability to fight pathogens and to clear infections. If this tender equilibrium is disturbed, severe chronic inflammatory reactions can result. Tolerogenic intestinal dendritic cells fulfil a crucial role in balancing immune responses and therefore creating homeostatic conditions and preventing from uncontrolled inflammation. Although several dendritic cell subsets have already been characterized to play a pivotal role in this process, less is known about definite molecular mechanisms of how intestinal dendritic cells are converted into tolerogenic ones. Here we review how gut commensal bacteria interact with intestinal dendritic cells and why this bacteria-host cell interaction is crucial for induction of dendritic cell tolerance in the intestine. Hereby, different commensal bacteria can have distinct effects on the phenotype of intestinal dendritic cells and these effects are mainly mediated by impacting toll-like receptor signalling in dendritic cells.

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“…For instance, the interaction between IAP and thrombospondin‐1 is proposed to be a key component of the regulatory circuit involving synovium‐derived cells and T lymphocytes, and perpetuates the inflammatory process in the rheumatoid joint . Alternatively, CD47/SIRPα interaction is linked to a phenotype of immature APC and the peripheral tolerance under steady state and pathological conditions . Moreover, prolonged inflammation has been demonstrated in the CD47‐deficient mice .…”

Section: Discussionmentioning

confidence: 99%

Cell surface markers and exogenously induced PpIX in synovial mesenchymal stem cells

et al. 2015

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The aim of present study was to assess the expression of surface markers and the accumulation of protoporphyrin IX in synovial mesenchymal stem cells (SMSCs). SMSC from patients with rheumatoid arthritis (RA, n = 5) and osteoarthritis (OA, n = 5-6) were characterized and their PpIX accumulation rates were evaluated by flow cytometry. The expression of the 21 out of 24 tested surface markers, related to stem-like features and aggressiveness of cells showed no statistically significant differences between RA and OA groups. However, the cells from RA group had the significantly lower levels of expression for the integrin-associated protein CD47 and the grow factor receptor CD271 (P = 0.018), while the higher levels of cell membrane zinc-dependent metalloproteinase CD10 (P = 0.006), as compared to the cells from OA group. Comparison of the mean intensities of PpIX fluorescence revealed no statistically significant differences between the RA and OA groups, as well as no relation to proliferation rates or cell size, although some conspicuous distinction in PpIX accumulation was observed in certain specimens within these groups, suggesting possibilities of this method application for characterization of individual SMSC populations. CD10, CD47, and CD271 were differently expressed in RA and OA SMSC, while had no direct association with the PpIX fluorescence intensity.

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Novel CD47: SIRPα Dependent Mechanism for the Activation of STAT3 in Antigen-Presenting Cell

Cited by 19 publications

References 43 publications

The influence of hypoxia and IFN-γ on the proteome and metabolome of therapeutic mesenchymal stem cells

The influence of hypoxia and IFN-γ on the proteome and metabolome of therapeutic mesenchymal stem cells

Molecular Mechanisms of Induction of Tolerant and Tolerogenic Intestinal Dendritic Cells in Mice

Cell surface markers and exogenously induced PpIX in synovial mesenchymal stem cells

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