Liver transplantation immunology: Immunosuppression, rejection, and immunomodulation

Montano‐Loza, Aldo J.; Rodríguez‐Perálvarez, Manuel; Pageaux, G.-P.; Sánchez‐Fueyo, Alberto; Feng, Sandy

doi:10.1016/j.jhep.2023.01.030

Cited by 40 publications

(22 citation statements)

References 156 publications

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“…Interestingly, the monocytes from ACR patients also showed an enhanced differentiation capacity in phase 2, as indicated by the increased diversity of monocytes, such as the increased proportions of CD14 + FOS + monocytes and CD14 + AP-1 + monocytes. The relatively strong immune responses within 90 days after LT may explain at least in part why the tacrolimus medication guideline recommends potent target tacrolimus trough concentration 56 , 57 and why acute rejections usually occur within the first 3 months after LT. 66 , 67 All of these findings in phases 2 and 3 indicate that LT patients are more susceptible to acute rejection in these phases, and the FOS-expressing monocytes in phase 2 and inflamed NK cells spanning from phases 2 to 3 may be predictive biomarkers and potential therapeutic targets for clinical management and graft rejection.…”

Section: Discussionmentioning

confidence: 96%

Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

Wang,

Peng,

Yuan

et al. 2024

The Innovation

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Section: Discussionmentioning

confidence: 96%

Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

Wang,

Peng,

Yuan

et al. 2024

The Innovation

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“…The activation of T cells by APCs also encompasses a semi‐indirect pathway. This pathway involves T cell activation signaling, costimulatory receptors on T cells (CD28, CD40), corresponding ligands on APCs (CD40L, CD80, CD86), and the microenvironment that triggers T cell activation 260 . KCs also mediates the T cell response and secondary apoptosis of other immune cells through cytokines 261,262 .…”

Section: Immune Response To Armentioning

confidence: 99%

Role of the immune system in liver transplantation and its implications for therapeutic interventions

Chen,

Hu,

Huang

et al. 2023

MedComm

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Liver transplantation (LT) stands as the gold standard for treating end‐stage liver disease and hepatocellular carcinoma, yet postoperative complications continue to impact survival rates. The liver's unique immune system, governed by a microenvironment of diverse immune cells, is disrupted during processes like ischemia–reperfusion injury posttransplantation, leading to immune imbalance, inflammation, and subsequent complications. In the posttransplantation period, immune cells within the liver collaboratively foster a tolerant environment, crucial for immune tolerance and liver regeneration. While clinical trials exploring cell therapy for LT complications exist, a comprehensive summary is lacking. This review provides an insight into the intricacies of the liver's immune microenvironment, with a specific focus on macrophages and T cells as primary immune players. Delving into the immunological dynamics at different stages of LT, we explore the disruptions after LT and subsequent immune responses. Focusing on immune cell targeting for treating liver transplant complications, we provide a comprehensive summary of ongoing clinical trials in this domain, especially cell therapies. Furthermore, we offer innovative treatment strategies that leverage the opportunities and prospects identified in the therapeutic landscape. This review seeks to advance our understanding of LT immunology and steer the development of precise therapies for postoperative complications.

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“…They found that peripheral blood Treg in the immune-tolerant group was first enriched after LT followed by a remarkable decay, but no Treg enrichment was observed in the immune rejection patients. Additionally, Aldo et al proposed to rule out the immune rejection based on ALT levels, serum donor-specific HLA antibodies, and liver stiffness by FibroScan [82]. Although many non-invasive biomarkers of immune tolerance have been proposed, future studies are required to validate their efficiency.…”

Section: Immune Tolerance Biomarkersmentioning

confidence: 99%

Immunomodulatory Role of Mesenchymal Stem Cells in Liver Transplantation: Status and Prospects

Li,

Yu,

Chen

et al. 2023

Dig Dis

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Background: Liver transplantation (LT) is the only effective therapy for end-stage liver diseases, but some patients usually present with serious infection and immune rejection. Those with immune rejection require long-term administration of immunosuppressants, leading to serious adverse effects. Mesenchymal stem cells (MSCs) have various advantages in immune regulation and are promising drugs most likely to replace immunosuppressants. Summary: This study summarized the application of MSCs monotherapy, its combination with immunosuppressants, MSCs genetic modification, and MSCs derivative therapy (cell-free therapy) in LT. This may deepen the understanding of immunomodulatory role of MSCs and promote the application of MSCs in immune rejection treatment after LT. Key messages: MSCs could attenuate ischemia-reperfusion injury and immune rejection. There is no consensus on the effects of types and concentrations of immunosuppressants on MSCs. Although genetically modified MSCs have contributed to better outcomes to some extent, the best modification is still unclear. Besides, multiple clinical complications developed frequently after LT. Unfortunately, there are still few studies on the polygenic modification of MSCs for the simultaneous treatment of these complications. Therefore, more studies should be performed to investigate the potency of multi-gene modified MSCs in treating complications after LT. Additionally, MSC derivatives mainly include exosomes, extracellular vesicles, and conditioned medium. Despite therapeutic effects, these three therapies still have some limitations such as heterogeneity between generations and that they cannot be quantified accurately.

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Liver transplantation immunology: Immunosuppression, rejection, and immunomodulation

Cited by 40 publications

References 156 publications

Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

Role of the immune system in liver transplantation and its implications for therapeutic interventions

Immunomodulatory Role of Mesenchymal Stem Cells in Liver Transplantation: Status and Prospects

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