Rapid activation and hepatic recruitment of innate-like regulatory B cells after invariant NKT cell stimulation in mice

Almishri, Wagdi; Deans, Julie P.; Swain, Mark G.

doi:10.1016/j.jhep.2015.06.007

Cited by 16 publications

(30 citation statements)

References 52 publications

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“…Because both regulatory cell populations were notably lower in the spleens of α‐GalCer+MSC–treated mice (Supporting Fig. 1), we assumed that MSCs promoted migration of these regulatory cells from the spleen into the injured livers where they suppress inflammation …”

Section: Resultsmentioning

confidence: 99%

“…For Treg depletion, mice were injected intraperitoneally (IP) with cyclophosphamide (CY; Galenika A.D., Belgrade, Serbia) at a dose of 10 mg/kg or anti‐CD25 antibody (PC61 mitochondrial antibody, Sigma‐Aldrich, Munich, Germany) at a dose of 250 mg/mouse at 3 days before α‐GalCer injection . B cell depletion was accomplished by a single IP injection of anti‐mouse CD20 antibody (Clone 5D2, Genentech, Inc., San Francisco, CA) at a dose of 10 mg/kg, and the same isotype immunoglobulin was used for control …”

Section: Methodsmentioning

confidence: 99%

“…(14,18) B cell depletion was accomplished by a single IP injection of antimouse CD20 antibody (Clone 5D2, Genentech, Inc., San Francisco, CA) at a dose of 10 mg/kg, and the same isotype immunoglobulin was used for control. (19)…”

Section: Depletion Of Regulatory Cellsmentioning

confidence: 99%

“…1), we assumed that MSCs promoted migration of these regulatory cells from the spleen into the injured livers where they suppress inflammation. (19)…”

Section: Msc-dependent Attenuation Of Acute Liver Failure Is Accompanmentioning

confidence: 99%

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Crosstalk between mesenchymal stem cells and T regulatory cells is crucially important for the attenuation of acute liver injury

et al. 2018

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One of the therapeutic options for the treatment of fulminant hepatitis is repopulation of intrahepatic regulatory cells because their pool is significantly reduced during acute liver failure. Although it is known that mesenchymal stem cells (MSCs), which have beneficent effects in the therapy of fulminant hepatitis, may promote expansion of regulatory T cells (Tregs) and regulatory B cells (Bregs), the role of these regulatory cells in MSC-mediated attenuation of acute liver injury is unknown. Herewith, we described the molecular mechanisms involved in the crosstalk between MSCs and liver regulatory cells and analyzed the potential of MSC-based therapy for the expansion of intrahepatic regulatory cells in mouse model of acute liver failure. MSC-dependent attenuation of α-galactosylceramide (α-GalCer)-induced acute liver injury in mice was accompanied with an increased presence of interleukin (IL) 10-producing CD4 CD25 forkhead box P3 Tregs and IL10- and transforming growth factor β-producing marginal zone-like Bregs in the liver. Depletion of Bregs did not alter MSC-based alleviation of acute liver failure, whereas depletion of Tregs completely abrogated hepatoprotective effects of MSCs and inhibited their capacity to attenuate hepatotoxicity of liver natural killer T cells (NKTs), indicating that Tregs, and not Bregs, were critically involved in MSC-based modulation of acute liver inflammation. MSCs, in a paracrine, indoleamine 2,3-dioxygenase-dependent manner, significantly increased the capacity of Tregs to produce immunosuppressive IL10 and to suppress hepatotoxicity of liver NKTs. Accordingly, adoptive transfer of MSC-primed Tregs resulted in the complete attenuation of α-GalCer-induced acute liver failure. In conclusion, our findings highlighted the crucial importance of Tregs for MSC-based attenuation of acute liver failure and indicated the significance of MSC-mediated priming of Tregs as a new therapeutic approach in Treg-based therapy of acute liver injury. Liver Transplantation 24 687-702 2018 AASLD.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Depletion Of Regulatory Cellsmentioning

confidence: 99%

“…1), we assumed that MSCs promoted migration of these regulatory cells from the spleen into the injured livers where they suppress inflammation. (19)…”

Section: Msc-dependent Attenuation Of Acute Liver Failure Is Accompanmentioning

confidence: 99%

See 2 more Smart Citations

Crosstalk between mesenchymal stem cells and T regulatory cells is crucially important for the attenuation of acute liver injury

et al. 2018

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“…[62] The role of resident hepatic B cells was dissected in α-GalCer mediated liver injury demonstrating that iNKT cells stimulation and recruitment of innate-like regulatory B cells to the liver suppressed the liver inflammation. [63]…”

Section: α-Galactosylceramide (α-Galcer)-induced Acute Hepatitismentioning

confidence: 99%

Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance

Khan

Ahmad

Khan

et al. 2017

Hepatobiliary & Pancreatic Diseases International

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The role of the CD39–CD73–adenosine pathway in liver disease

Wang

Gao

Zhou

et al. 2020

Journal Cellular Physiology

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Extracellular adenosine triphosphate (ATP) is a danger signal released by dying and damaged cells, and it functions as an immunostimulatory signal that promotes inflammation. The ectonucleotidases CD39/ectonucleoside triphosphate diphosphohydrolase-1 and CD73/ecto-5′-nucleotidase are cell-surface enzymes that breakdown extracellular ATP into adenosine. This drives a shift from an ATP-driven proinflammatory environment to an anti-inflammatory milieu induced by adenosine. The CD39-CD73-adenosine pathway changes dynamically with the pathophysiological context in which it is embedded. Accumulating evidence suggests that CD39 and CD73 play important roles in liver disease as critical components of the extracellular adenosinergic pathway. Recent studies have shown that the modification of the CD39-CD73-adenosine pathway alters the liver's response to injury. Moreover, adenosine exerts different effects on the pathophysiology of the liver through different receptors. In this review, we aim to describe the role of the CD39-CD73-adenosine pathway and adenosine receptors in liver disease, highlighting potential therapeutic targets in this pathway, which will facilitate the development of therapeutic strategies for the treatment of liver disease.

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Rapid activation and hepatic recruitment of innate-like regulatory B cells after invariant NKT cell stimulation in mice

Cited by 16 publications

References 52 publications

Crosstalk between mesenchymal stem cells and T regulatory cells is crucially important for the attenuation of acute liver injury

Crosstalk between mesenchymal stem cells and T regulatory cells is crucially important for the attenuation of acute liver injury

Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance

The role of the CD39–CD73–adenosine pathway in liver disease

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