Innate allorecognition in transplantation

Abou-Daya, Khodor I.; Oberbarnscheidt, Martin H.

doi:10.1016/j.healun.2021.03.018

Cited by 19 publications

(10 citation statements)

References 59 publications

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“…Here we particularly focused on the induction of the expression of MHC class II and costimulatory CD80/86 on monocytes and macrophages, given the place of these cell types in the initiation of acute and chronic rejection of allografts [ 24 , 27 ]. This activation of recruited MoCs may lead to their differentiation in MPs and/or Mo-derived DCs, becoming potent antigen-presenting cells (APCs) for initiation of the T- and B-cell allo-responses [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

A cross-circulatory platform for monitoring innate allo-responses in lung grafts

et al. 2023

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Lung transplantation is the only curative option for end-stage chronic respiratory diseases. However the survival rate is only about 50% at 5 years. Although experimental evidences have shown that innate allo-responses impact on the clinical outcome, the knowledge of the involved mechanisms involved is limited. We established a cross-circulatory platform to monitor the early recruitment and activation of immune cells in an extracorporeal donor lung by coupling blood perfusion to cell mapping with a fluorescent marker in the pig, a commonly-used species for lung transplantation. The perfusing pig cells were easily detectable in lung cell suspensions, in broncho-alveolar lavages and in different areas of lung sections, indicating infiltration of the organ. Myeloid cells (granulocytes and monocytic cells) were the dominant recruited subsets. Between 6 and 10 h of perfusion, recruited monocytic cells presented a strong upregulation of MHC class II and CD80/86 expression, whereas alveolar macrophages and donor monocytic cells showed no significant modulation of expression. This cross-circulation model allowed us to monitor the initial encounter between perfusing cells and the lung graft, in an easy, rapid, and controllable manner, to generate robust information on innate response and test targeted therapies for improvement of lung transplantation outcome.

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Section: Discussionmentioning

confidence: 99%

A cross-circulatory platform for monitoring innate allo-responses in lung grafts

et al. 2023

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“…A proinflammatory response by fibroblasts in the context of microorganism infection can induce an innate immune response against microorganisms mediated by toll-like receptors (TLRs), antimicrobial peptides, proinflammatory cytokines and chemokines, and growth factors 34 , 62 , 63 . There is a growing body of evidence that monocytes and macrophages distinguish between self and allogeneic non-self 58 , 64 – 67 . It has been shown that polymorphism in the gene encoding signal regulatory protein α (SIRP-α), which binds to the monomorphic receptor, CD47, is essential for the monocyte allorecognition response in the marrow plug transplantation model 68 .…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Immune Responses Trigger Rejection of Allogeneic Fibroblasts Transplanted into Mouse Skin

Farrokhi

Rahavi

et al. 2022

Cell Transplant

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Fibroblasts, or their homolog stromal cells, are present in most tissues and play an essential role in tissue homeostasis and regeneration. As a result, fibroblast-based strategies have been widely employed in tissue engineering. However, while considered to have immunosuppressive properties, the survival and functionality of allogeneic fibroblasts after transplantation remain controversial. Here, we evaluated innate and adaptive immune responses against allogeneic fibroblasts following intradermal injection into different immune-deficient mouse strains. While allogeneic fibroblasts were rejected 1 week after transplantation in immunocompetent mice, rejection did not occur in immunodeficient γ chain–deficient NOD-SCID (NSG) mice. T-cell- and B-cell-deficient RAG1 knockout mice showed greater loss of fibroblasts by day 5 after transplantation compared with NSG mice ( P ≤ 0.05) but prolonged persistence compared with wild-type recipient ( P ≤ 0.005). Loss of fibroblasts correlated with the expression of proinflammatory chemokine genes and infiltration of myeloid cells in the transplantation site. Depletion of macrophages and neutrophils delayed rejection, revealing the role of innate immune cells in an early elimination of fibroblasts that is followed by T-cell-mediated rejection in the second week. These findings indicate that the application of allogeneic fibroblasts in tissue engineering products requires further improvements to overcome cell rejection by innate and adaptive immune cells.

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“…Several studies have implied the importance of NK cells in initiating allorecognition [64,68]. DSAs binding to endothelial cells may lead to the ligation of Fc receptors on NK cells and contribute to antibody-mediated cytotoxicity or to the release of proinflammatory cytokines, such as IFNγ.…”

Section: Nk Cellsmentioning

confidence: 99%

Failing Heart Transplants and Rejection—A Cellular Perspective

Hurskainen

Ainasoja

Lemström

2021

JCDD

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The median survival of patients with heart transplants is relatively limited, implying one of the most relevant questions in the field—how to expand the lifespan of a heart allograft? Despite optimal transplantation conditions, we do not anticipate a rise in long-term patient survival in near future. In order to develop novel strategies for patient monitoring and specific therapies, it is critical to understand the underlying pathological mechanisms at cellular and molecular levels. These events are driven by innate immune response and allorecognition driven inflammation, which controls both tissue damage and repair in a spatiotemporal context. In addition to immune cells, also structural cells of the heart participate in this process. Novel single cell methods have opened new avenues for understanding the dynamics driving the events leading to allograft failure. Here, we review current knowledge on the cellular composition of a normal heart, and cellular mechanisms of ischemia-reperfusion injury (IRI), acute rejection and cardiac allograft vasculopathy (CAV) in the transplanted hearts. We highlight gaps in current knowledge and suggest future directions, in order to improve cellular and molecular understanding of failing heart allografts.

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Innate allorecognition in transplantation

Cited by 19 publications

References 59 publications

A cross-circulatory platform for monitoring innate allo-responses in lung grafts

A cross-circulatory platform for monitoring innate allo-responses in lung grafts

Inflammatory Immune Responses Trigger Rejection of Allogeneic Fibroblasts Transplanted into Mouse Skin

Failing Heart Transplants and Rejection—A Cellular Perspective

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