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

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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… Click to show full abstract

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. CLAD is the end-stage of a disease continuum marked by complex, interacting, innate and adaptive, cellular and humoral, allo- and autoimmune mechanisms, repeated lung injury, tissue remodelling and repair, ultimately leading to allograft dysfunction. https://bit.ly/3Ny3LZz

Keywords: allograft dysfunction; lung; allograft; lung allograft; chronic lung

Journal Title: European Respiratory Review
Year Published: 2022

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