Publication: Extracellular ATP activates the NLRP3 inflammasome and is an early danger signal of skin allograft rejection
Authors
Amores-Iniesta, Joaquín ; Barberá-Cremades, Maria ; Pons, José A. ; Revilla-Nuín, Beatriz ; Martínez-Alarcón, Laura ; Di Virgilio, Francesco ; Parrilla, Pascual ; Baroja-Mazo, Alberto ; Martínez Cáceres, Carlos Manuel ; Pelegrín Vivancos, Pablo
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Publisher
Cell Press
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DOI
10.1016/j.celrep.2017.11.079
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info:eu-repo/semantics/article
Description
©2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the Accepted, version of a Published Work that appeared in final form in Cell Report. To access the final edited and published work see 10.1016/j.celrep.2017.11.079
Abstract
Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18. This process is a necessary stage in the deleterious Th1 response against allotransplantation via interferon-g production. Lack of IL-18 resulted in a decrease in graft- infiltrated CD8 cells, but an increase in regulatory T cells. In human liver transplant patients subjected to progressive immunosuppressive drug withdrawal, we found that patients suffering acute rejection had higher levels of the P2X7 receptor in circulating inflammatory monocytes compared to tolerant patients. These data suggest that the pharmacological inhibition of the P2X7 receptor or the NLRP3 inflammasome will aid in inducing transplant tolerance without complete immunoparalysis.
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Citation
Cell Report, volumen 21, volumen 12, año 2017, páginas 3414-3426.
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