Lung transplantation: Chronic allograft dysfunction and establishing immune tolerance

Gracon, Adam; Wilkes, David S.

doi:10.1016/j.humimm.2014.06.015

Cited by 15 publications

(19 citation statements)

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“…This effect might play an important role in critically modifying the process of PGD early after transplantation [ 37 ]. The innate immune system is also involved in the etiology of bronchiolitis obliterans syndrome (BOS) [ 38 ], and therefore MAPC cell administration early in the process of lung transplantation might have an effect on the development of BOS, the main predictor of long-term outcome. Further experiments will have to elucidate the effect of MAPC cell administration on graft function after transplantation.…”

Section: Discussionmentioning

confidence: 99%

Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model

et al. 2017

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BackgroundPrimary graft dysfunction (PGD) is considered to be the end result of an inflammatory response targeting the new lung allograft after transplant. Previous research has indicated that MAPC cell therapy might attenuate this injury by its paracrine effects on the pro-/anti-inflammatory balance. This study aims to investigate the immunoregulatory capacities of MAPC cells in PGD when administered in the airways.MethodsLungs of domestic pigs (n = 6/group) were subjected to 90 minutes of warm ischemia. Lungs were cold flushed, cannulated on ice and placed on EVLP for 6 hours. At the start of EVLP, 40 ml of an albumin-plasmalyte mixture was distributed in the airways (CONTR group). In the MAPC cell group, 150 million MAPC cells (ReGenesys/Athersys, Cleveland, OH, USA) were added to this mixture. At the end of EVLP, a physiological evaluation (pulmonary vascular resistance, lung compliance, PaO2/FiO2), wet-to-dry weight ratio (W/D) sampling and a multiplex analysis of bronchoalveolar lavage (BAL) (2 × 30 ml) was performed.ResultsPulmonary vascular resistance, lung compliance, PaO2/FiO2 and W/D were not statistically different at the end of EVLP between both groups. BAL neutrophilia was significantly reduced in the MAPC cell group. Moreover, there was a significant decrease in TNF-α, IL-1β and IFN-γ in the BAL, but not in IFN-α; whereas IL-4, IL-10 and IL-8 were below the detection limit.ConclusionsAlthough no physiologic effect of MAPC cell distribution in the airways was detected during EVLP, we observed a reduction in pro-inflammatory cytokines and neutrophils in BAL in the MAPC cell group. This effect on the innate immune system might play an important role in critically modifying the process of PGD after transplantation. Further experiments will have to elucidate the immunoregulatory effect of MAPC cell administration on graft function after transplantation.

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Section: Discussionmentioning

confidence: 99%

Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model

et al. 2017

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“…Tregs are essential components of the normal immune system and are responsible for maintaining homeostasis and balance activated immune responses. This is accomplished by the release of immunosuppressive cytokines (TGF-β, IL-10) as well as direct cell-cell interactions (e.g., regulation of dendritic cell maturation and function) [11]. These actions prevent excessive effector T-cell responses [14].…”

Section: Immune Processes In Clad T-cell-mediated Immunitymentioning

confidence: 99%

Immune processes in the pathogenesis of chronic lung allograft dysfunction: identifying the missing pieces of the puzzle

et al. 2022

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Lung transplantation is the optimal treatment for selected patients with end-stage chronic lung diseases. However, chronic lung allograft dysfunction remains the leading obstacle to improved long-term outcomes. Traditionally, lung allograft rejection has been considered primarily as a manifestation of cellular immune responses. However, in reality, an array of complex, interacting and multifactorial mechanisms contribute to its emergence. Alloimmune-dependent mechanisms, including T-cell-mediated rejection and antibody-mediated rejection, as well as non-alloimmune injuries, have been implicated. Moreover, a role has emerged for autoimmune responses to lung self-antigens in the development of chronic graft injury. The aim of this review is to summarise the immune processes involved in the pathogenesis of chronic lung allograft dysfunction, with advanced insights into the role of innate immune pathways and crosstalk between innate and adaptive immunity, and to identify gaps in current knowledge.

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“…Nevertheless, while minimal immune response can protect against antibody formation and subsequent rejection, a complete BLATTER AND SWEET lack of immune response puts transplant patients at risk for infection. One of the ultimate goals of studying AMR will be to identify mechanisms of immune tolerance, 26 a state in which immunosuppression could be lessened because the lung allograft would no longer be recognized as foreign.…”

Section: Lung Transplantation In Cystic Fibrosismentioning

confidence: 99%

Lung Transplantation in Cystic Fibrosis: Trends and Controversies

Blatter

Sweet

2015

Pediatric Allergy, Immunology, and Pulmonology

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Lung transplantation: Chronic allograft dysfunction and establishing immune tolerance

Cited by 15 publications

References 91 publications

Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model

Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model

Immune processes in the pathogenesis of chronic lung allograft dysfunction: identifying the missing pieces of the puzzle

Lung Transplantation in Cystic Fibrosis: Trends and Controversies

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