Hepatic immune regulation by stromal cells

Schildberg, Frank A.; Sharpe, Arlene H.; Turley, Shannon J.

doi:10.1016/j.coi.2014.10.002

Cited by 22 publications

(17 citation statements)

References 51 publications

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“…T cell stimulation (83)(84)(85)(86)(87)(88). They can also induce CD8 T cell apoptosis by Fas-FasL interaction, as described for KCs following reactive-oxygen species (ROS) production induced by FasL upregulation on their surface (80,89), and for HSCs through induction of intracellular signaling pathways triggered by PD-L1 and B7-H4 crosslinking (90)(91)(92)(93).…”

Section: Tolerogenic Apcmentioning

confidence: 99%

Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches

et al. 2020

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Section: Tolerogenic Apcmentioning

confidence: 99%

Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches

et al. 2020

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“…The tolerogenic properties of livers suggest that, as in kidneys, cells or cell products intrinsic to the organ are important. Three cell populations present in liver have been shown capable of suppressing an alloimmune response; 1) pDCs, located within periportal areas and around central veins (95), 2) liver sinusoidal endothelial cells (LSECs) that generate anti-inflammatory cytokines (96) and diminish the survival of CD8+ T cells (97-99) and 3) hepatic stellate cells (HSCs) that can induce Tregs (100,101). …”

Section: Introductionmentioning

confidence: 99%

Organ-specific differences in achieving tolerance

Madariaga¹,

Kreisel

Madsen

2015

Current Opinion in Organ Transplantation

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Purpose of review When it comes to tolerance induction, kidney allografts behave differently from heart allografts which behave differently from lung allografts. Here, we examine how and why different organ allografts respond differently to the same tolerance induction protocol. Recent findings Allograft tolerance has been achieved in experimental and clinical kidney transplantation. However, inducing tolerance in experimental recipients of heart and lung allografts has proven to be more challenging. New protocols being developed in nonhuman primates based on mixed chimerism and co-transplantation of tolerogenic organs may provide mechanistic insights to help overcome these challenges. Summary Tolerance induction protocols that are successful in patients transplanted with “tolerance-prone” organs such as kidneys and livers will most likely not succeed in recipients of “tolerance-resistant” organs such as hearts and lungs. Separate clinical trials using more robust tolerance protocols will be required to achieve tolerance in heart and lung recipients.

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“…The liver therefore constitutes a set of inflammation-resistant mechanisms that finely regulate the immune response to innocent antigens [ 2 ]. Among these mechanisms, liver stroma contributes to the establishment of liver tolerance [ 33 ], but how stromal cells exert suppression remains poorly understood. Here, we found that the liver stroma programs mDCs to proliferate and differentiate into DCregs, inducing phenotypic changes as described previously [ 16 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Hepatic stroma-educated regulatory DCs suppress CD8+ T cell proliferation in mice

Wang

DongWei

et al. 2017

Oncotarget

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Liver dendritic cells (DCs) display immunosuppressive activities and inhibit the CD4+ T cell response. The present study assessed whether and how liver DCs suppress CD8+ T cells. We found that bone marrow-derived mature DCs incubated with liver stromal cells were characterized by a longer life span, reduced CD11c, IA/IE, CD80, CD86, and CD40 expression, and increased CD11b expression. These unique liver stromal cell-educated mature DCs (LSed-DCs) stimulated CD8+ T cells to express CD25 and CD69, but inhibited their proliferation. CD8+ T cell suppression depended on soluble factors released by LSed-DCs, but not cell-cell contact. Compared with mature DCs, LSed-DCs produced more nitric oxide and IL-10. Addition of a nitric oxide synthase inhibitor, PBIT, but not an IL-10-blocking mAb, reversed LSed-DC inhibition of CD8+ T cell proliferation. We also found that LSed-DCs reduced CD8+ T cell-mediated liver damage in a mouse model of autoimmune hepatitis. These results demonstrate that the liver stroma induces mature DCs to differentiate into regulatory DCs that suppress CD8+ T cell proliferation, and thus contribute to liver tolerance.

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Hepatic immune regulation by stromal cells

Cited by 22 publications

References 51 publications

Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches

Pathogenetic Mechanisms of T Cell Dysfunction in Chronic HBV Infection and Related Therapeutic Approaches

Organ-specific differences in achieving tolerance

Hepatic stroma-educated regulatory DCs suppress CD8+ T cell proliferation in mice

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